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  • 1.
    Andersson, Eva
    et al.
    Sahlgrens University Hospital, Sweden .
    Westberg, Hakan
    Örebro University Hospital, Sweden .
    Bryngelsson, Ing-Liss
    Örebro University Hospital, Sweden .
    Magnuson, Anders
    Örebro University Hospital, Sweden .
    Persson, Bodil
    Linköping University, Department of Clinical and Experimental Medicine, Occupational and Environmental Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Occupational and Environmental Medicine Center.
    Cancer incidence among Swedish pulp and paper mill workers: a cohort study of sulphate and sulphite mills2013In: International Archives of Occupational and Environmental Health, ISSN 0340-0131, E-ISSN 1432-1246, Vol. 86, no 5, p. 529-540Article in journal (Refereed)
    Abstract [en]

    Associations between various malignancies and work in the pulp and paper industry have been reported but mostly in analyses of mortality rather than incidence. We aimed to study cancer incidence by main mill pulping process, department and gender in a Swedish cohort of pulp and paper mill workers. The cohort (18,113 males and 2,292 females, enrolled from 1939 to 1999 with greater than 1 year of employment) was followed up for cancer incidence from 1958 to 2001. Information on the workers department and employment was obtained from the mills personnel files, and standardized incidence ratios (SIRs) were calculated using the Swedish population as reference. Overall cancer incidence, in total 2,488 cases, was not increased by work in any department. However, risks of pleural mesothelioma were increased among males employed in sulphate pulping (SIR, 8.38; 95 % CI, 3.37-17) and maintenance (SIR, 6.35; 95 % CI, 3.47-11), with no corresponding increase of lung cancer. Testicular cancer risks were increased among males employed in sulphate pulping (SIR, 4.14; 95 % CI, 1.99-7.61) and sulphite pulping (SIR, 2.59; 95 % CI, 0.95-5.64). Female paper production workers showed increased risk of skin tumours other than malignant melanoma (SIR, 2.92; 95 % CI, 1.18-6.02). Incidence of pleural mesothelioma was increased in the cohort, showing that asbestos exposure still has severe health consequences, and highlighting the exigency of strict asbestos regulations and elimination. Testicular cancer was increased among pulping department workers. Shift work and endocrine disruptors could be of interest in this context.

  • 2.
    Bäckryd, Emmanuel
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
    Ghafouri, Bijar
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center. Östergötlands Läns Landsting, Heart and Medicine Center, Occupational and Environmental Medicine Center.
    Larsson, Britt
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Pain and Rehabilitation Centre.
    Gerdle, Björn
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
    Do low levels of Beta-endorphin in the cerebrospinal fluid indicate defective top-down inhibition in patients with chronic neuropathic pain? A cross-sectional, comparative study2014In: Pain medicine (Malden, Mass.), ISSN 1526-2375, E-ISSN 1526-4637, Vol. 15, no 1, p. 111-119Article in journal (Refereed)
    Abstract [en]

    Objective

    Pain medicine still lacks mechanism-specific biomarkers to guide diagnosis and treatment, and defective top-down modulation is an important factor in the pathophysiology of chronic pain conditions. Using modern analytical tools and advanced multivariate statistical analysis, the aim of this study was to revisit two classical potential biomarkers of pro- and anti-nociception in humans (substance P and beta-endorphin), focusing particularly on the cerebrospinal fluid (CSF).

    Design

    Cross-sectional, comparative, observational study.

    Subjects

    Patients with chronic, post-traumatic and/or post-surgical, neuropathic pain refractory to conventional treatment (N = 15) and healthy controls (N = 19) were included.

    Methods

    Samples were taken from CSF and blood, and levels of substance P and beta-endorphin were investigated using a Luminex technology kit.

    Results

    We found low levels of beta-endorphin in the CSF of neuropathic pain patients (66 ± 11 pcg/mL) compared with healthy controls (115 ± 14 pcg/mL) (P = 0.017). Substance P levels in the CSF did not differ (20 ± 2 pcg/mL, 26 ± 2, P = 0.08). However, our multivariate data analysis showed that belonging to the patient group was associated with low levels of both substances in the CSF. A higher correlation between the levels of beta-endorphin and substance P in CSF was found in healthy controls than in patients (rs = 0.725, P < 0.001 vs rs = 0.574, P = 0.032).

    Conclusions

    Patients with chronic neuropathic pain due to trauma or surgery had low levels of beta-endorphin in the CSF. We speculate that this could indicate a defective top-down modulation of pain in chronic neuropathic pain. Our results also illustrate the importance of taking a system-wide, multivariate approach when searching for biomarkers.

  • 3.
    Dawson, Andreas
    et al.
    Malmö University, Sweden.
    Ghafouri, Bijar
    Linköping University, Department of Medical and Health Sciences, Rehabilitation Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center. Östergötlands Läns Landsting, Heart and Medicine Center, Occupational and Environmental Medicine Center.
    Gerdle, Björn
    Linköping University, Department of Medical and Health Sciences, Rehabilitation Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
    List, Thomas
    Malmö University, Sweden.
    Svensson, Peter
    Aarhus University, Denmark.
    Ernberg, Malin
    Karolinska Institutet, Huddinge, Sweden.
    Pain and intramuscular release of algesic substances in the masseter muscle after experimental tooth-clenching exercises in healthy subjects2013In: Journal of Orofacial Pain, ISSN 1064-6655, E-ISSN 1945-3396, Vol. 27, no 4, p. 350-360Article in journal (Refereed)
    Abstract [en]

    AIMS:

    To investigate whether experimental tooth clenching leads to a release of algesic substances in the masseter muscle.

    METHODS:

    Thirty healthy subjects (16 females, 14 males) participated. During two sessions, separated by at least 1 week, intramuscular microdialysis was performed to collect masseter muscle 5-hydroxytryptamine (5-HT) and glutamate as well as the metabolic markers pyruvate and lactate. Two hours after the start of microdialysis, participants were randomized to a 20-min repetitive experimental tooth-clenching task (50% of maximal voluntary contraction) or a control session (no clenching). Pain and fatigue were measured throughout. The Friedman and Wilcoxon tests were used for statistical analyses.

    RESULTS:

    No alterations were observed in the concentrations of 5-HT, glutamate, pyruvate, and lactate over time in the clenching or control session, or between sessions at various time points. Pain (P < .01) and fatigue (P < .01) increased significantly over time in the clenching session and were significantly higher after clenching than in the control session (P < .01).

    CONCLUSION:

    Low levels of pain and fatigue developed with this experimental tooth-clenching model, but they were not associated with an altered release of 5-HT, glutamate, lactate, or pyruvate. More research is required to elucidate the peripheral release of algesic substances in response to tooth clenching.

  • 4.
    Ernberg, M.
    et al.
    Karolinska Institutet, Huddinge, Sweden.
    Castrillon, E.E.
    Aarhus University, Denmark.
    Ghafouri, Bijar
    Linköping University, Department of Medical and Health Sciences, Rehabilitation Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Sinnescentrum, Pain and Rehabilitation Centre. Östergötlands Läns Landsting, Heart and Medicine Centre, Occupational and Environmental Medicine Centre.
    Larsson, Britt
    Linköping University, Department of Medical and Health Sciences, Rehabilitation Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Sinnescentrum, Pain and Rehabilitation Centre.
    Gerdle, Björn
    Linköping University, Department of Medical and Health Sciences, Rehabilitation Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Sinnescentrum, Pain and Rehabilitation Centre.
    List, T.
    Malmö University, Sweden.
    Svensson, P.
    Aarhus University and Aarhus University Hospital, Denmark.
    Experimental myalgia induced by repeated infusion of acidicsaline into the human masseter muscle does not cause the release of algesic substances2013In: European Journal of Pain, ISSN 1090-3801, E-ISSN 1532-2149, Vol. 17, no 4, p. 539-550Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    Animal studies have shown that two repeated intramuscular injections of acidic saline induce mechanical allodynia that lasts for 4 weeks with spread to the contralateral side. In this study, we tested the hypothesis that two repeated intramuscular infusions of acidic saline into the human masseter muscle is associated with pain, mechanical allodynia and release of algesic substances. Eighteen healthy volunteers participated. On day 1, 2.5 mL of acidic saline (pH 3.3) was infused into one of the masseter muscles and isotonic saline (pH 6.0) into the other (randomized and single-blind). Two days later, intramuscular microdialysis was performed to sample serotonin, glutamate, pyruvate, lactate and glucose, during which the saline infusions were repeated. Pain and pressure pain thresholds (PPTs) were recorded before and after infusions on both days.

    RESULTS:

    Pain intensity induced by the infusions was higher after acidic than that after isotonic saline (p < 0.05). PPTs were decreased on both sides after microdialysis compared with baseline day 1 (p's < 0.05), but there were no differences in PPTs between sides at any time point. The levels of serotonin, glutamate, pyruvate, lactate or glucose did not change significantly during microdialysis.

    CONCLUSION:

    Infusion of acidic saline caused low levels of muscle pain, but no mechanical allodynia and no increased release of algesic substances. The value of this model appears modest, but future studies could be performed with larger sample size and higher flow rate before definite conclusions about the validity of the model for craniofacial myalgia can be drawn.

  • 5.
    Fornander, Louise
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Work and Environmental Science.
    Ghafouri, Bijar
    Linköping University, Department of Clinical and Experimental Medicine, Rehabilitation Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Occupational and Environmental Medicine Centre. Östergötlands Läns Landsting, Sinnescentrum, Pain and Rehabilitation Centre.
    Kihlström, Erik
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Microbiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Diagnostics, Department of Clinical Microbiology.
    Åkerlind, Britt
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Microbiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Diagnostics, Department of Clinical Microbiology.
    Schön, Thomas
    Kalmar County Hospital.
    Tagesson, Christer
    Linköping University, Department of Clinical and Experimental Medicine, Occupational and Environmental Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Occupational and Environmental Medicine Centre.
    Lindahl, Mats
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Work and Environmental Science.
    Innate immunity proteins and a new truncated form of SPLUNC1 in nasopharyngeal aspirates from infants with respiratory syncytial virus infection2011In: PROTEOMICS CLINICAL APPLICATIONS, ISSN 1862-8346, Vol. 5, no 9-10, p. 513-522Article in journal (Refereed)
    Abstract [en]

    Purpose: Respiratory syncytial virus (RSV) is the most common cause of severe respiratory tract infection in infants. The aim was to identify host defence components in nasopharyngeal aspirate (NPA) from infants with RSV infection and to study the expression of the novel 25 kDa innate immunity protein SPLUNC1. less thanbrgreater than less thanbrgreater thanExperimental design: NPAs from infants were analyzed with 2-DE and MS in a pilot study. The levels of SPLUNC1 were analyzed with immunoblotting in 47 NPAs, admitted for RSV diagnosis. less thanbrgreater than less thanbrgreater thanResults: Totally, 35 proteins were identified in NPA, including several innate immunity proteins such as group X phospholipase A(2), different S100 proteins and SPLUNC1. In addition, a new truncated 15 kDa form of SPLUNC1 was identified that was detected in about 50% of the aspirates admitted for RSV diagnosis. RSV-positive boys had significantly less 25 kDa SPLUNC1 than RSV-negative boys while there were no significant differences among girls. less thanbrgreater than less thanbrgreater thanConclusions and clinical relevance: Several important innate immunity proteins were identified in NPA. Notably, a new truncated form of the newly suggested anti-bacterial protein SPLUNC1 was found. It is possible that a decrease in SPLUNC1 in the upper airways may increase the risk for severe pneumonia in boys.

  • 6.
    Fornander, Louise
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Occupational and Environmental Medicine. Linköping University, Faculty of Health Sciences.
    Ghafouri, Bijar
    Linköping University, Department of Medical and Health Sciences, Rehabilitation Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center. Östergötlands Läns Landsting, Heart and Medicine Center, Occupational and Environmental Medicine Center.
    Lindahl, Mats
    Linköping University, Department of Clinical and Experimental Medicine, Occupational and Environmental Medicine. Linköping University, Faculty of Health Sciences.
    Graff, Pål
    Linköping University, Department of Clinical and Experimental Medicine, Work and Environmental Science. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Occupational and Environmental Medicine Center.
    Airway irritation among indoor swimming pool personnel: trichloramine exposure, exhaled NO and protein profiling of nasal lavage fluids2013In: International Archives of Occupational and Environmental Health, ISSN 0340-0131, E-ISSN 1432-1246, Vol. 86, no 5, p. 571-580Article in journal (Refereed)
    Abstract [en]

    Purpose

    Occurrence of airway irritation among indoor swimming pool personnel was investigated. The aims of this study were to assess trichloramine exposure levels and exhaled nitric oxide in relation to the prevalence of airway symptoms in swimming pool facilities and to determine protein effects in the upper respiratory tract.

    Methods

    The presence of airway symptoms related to work was examined in 146 individuals working at 46 indoor swimming pool facilities. Levels of trichloramine, as well as exhaled nitric oxide, were measured in five facilities with high prevalence of airway irritation and four facilities with no airway irritation among the personnel. Nasal lavage fluid was collected, and protein profiles were determined by a proteomic approach.

    Results

    17 % of the swimming pool personnel reported airway symptoms related to work. The levels of trichloramine in the swimming pool facilities ranged from 0.04 to 0.36 mg/m3. There was no covariance between trichloramine levels, exhaled nitric oxide and prevalence of airway symptoms. Protein profiling of the nasal lavage fluid showed that the levels alpha-1-antitrypsin and lactoferrin were significantly higher, and S100-A8 was significantly lower in swimming pool personnel.

    Conclusions

    This study confirms the occurrence of airway irritation among indoor swimming pool personnel. Our results indicate altered levels of innate immunity proteins in the upper airways that may pose as potential biomarkers. However, swimming pool facilities with high prevalence of airway irritation could not be explained by higher trichloramine exposure levels. Further studies are needed to clarify the environmental factors in indoor swimming pools that cause airway problems and affect the immune system.

  • 7.
    Fornander, Louise
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Occupational and Environmental Medicine. Linköping University, Faculty of Health Sciences.
    Graff, Pål
    Linköping University, Department of Clinical and Experimental Medicine, Occupational and Environmental Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Occupational and Environmental Medicine Center.
    Wåhlén, Karin
    Linköping University, Department of Clinical and Experimental Medicine, Occupational and Environmental Medicine. Linköping University, Faculty of Health Sciences.
    Ydreborg, Kjell
    County Hospital Ryhov, Jönköping, Sweden.
    Flodin, Ulf
    Linköping University, Department of Clinical and Experimental Medicine, Occupational and Environmental Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Occupational and Environmental Medicine Center.
    Leanderson, Per
    Linköping University, Department of Clinical and Experimental Medicine, Occupational and Environmental Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Occupational and Environmental Medicine Center.
    Lindahl, Mats
    Linköping University, Department of Clinical and Experimental Medicine, Occupational and Environmental Medicine. Linköping University, Faculty of Health Sciences.
    Ghafouri, Bijar
    Linköping University, Department of Medical and Health Sciences, Rehabilitation Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center. Östergötlands Läns Landsting, Heart and Medicine Center, Occupational and Environmental Medicine Center.
    Airway symptoms and biological markers in nasal lavage fluid in subjects exposed to metalworking fluids2013In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 8, no 12, p. e83089-Article in journal (Refereed)
    Abstract [en]

    BACKGROUNDS: Occurrence of airway irritation among industrial metal workers was investigated. The aims were to study the association between exposures from water-based metal working fluids (MWF) and the health outcome among the personnel, to assess potential effects on the proteome in nasal mucous membranes, and evaluate preventive actions.

    METHODS: The prevalence of airway symptoms related to work were examined among 271 metalworkers exposed to MWF and 24 metal workers not exposed to MWF at the same factory. At the same time, air levels of potentially harmful substances (oil mist, morpholine, monoethanolamine, formaldehyde) generated from MWF was measured. Nasal lavage fluid was collected from 13 workers and 15 controls and protein profiles were determined by a proteomic approach.

    RESULTS: Airway symptoms were reported in 39% of the workers exposed to MWF although the measured levels of MWF substances in the work place air were low. Highest prevalence was found among workers handling the MWF machines but also those working in the same hall were affected. Improvement of the ventilation to reduce MWF exposure lowered the prevalence of airway problems. Protein profiling showed significantly higher levels of S100-A9 and lower levels of SPLUNC1, cystatin SN, Ig J and β2-microglobulin among workers with airway symptoms.

    CONCLUSIONS: This study confirms that upper airway symptoms among metal workers are a common problem and despite low levels of MWF-generated substances, effects on airway immune proteins are found. Further studies to clarify the role of specific MWF components in connection to airway inflammation and the identified biological markers are warranted.

  • 8.
    Gerdle, Björn
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
    Ghafouri, Bijar
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center. Östergötlands Läns Landsting, Heart and Medicine Center, Occupational and Environmental Medicine Center.
    Ernberg, Malin
    Karolinska Institutet, Huddinge, Sweden.
    Larsson, Britt
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
    Chronic musculoskeletal pain: review of mechanisms and biochemical biomarkers as assessed by the microdialysis technique2014In: Journal of Pain Research, ISSN 1178-7090, E-ISSN 1178-7090, Vol. 7, p. 313-326Article, review/survey (Refereed)
    Abstract [en]

    Chronic musculoskeletal pain conditions are multifaceted, and approximately 20% of the adult population lives with severe chronic pain, with a higher prevalence in women and in lower income groups. Chronic pain is influenced by and interacts with physical, emotional, psychological, and social factors, and a biopsychosocial framework is increasingly applied in clinical practice. However, there is still a lack of assessment procedures based on the activated neurobiological pain mechanisms (ie, the biological part of the biopsychosocial model of pain), which may be a necessary step for further optimizing outcomes after treatments for patients with chronic pain. It has been suggested that chronic pain conditions are mainly driven by alterations in the central nervous system with little or no peripheral stimuli or nociception. In contrast, other authors argue that such central alterations are driven by peripheral alterations and nociceptive input. Microdialysis is an in vivo method for studying local tissue alterations and allows for sampling of substances in the interstitium of the muscle, where nociceptor free nerve endings are found close to the muscle fibers. The extracellular matrix plays a key role in physiologic functions of cells, including the primary afferent nociceptor. The present review mainly concerns the results of microdialysis studies and how they can contribute to the understanding of activated peripheral nociceptive and pain mechanisms in humans with chronic pain. The primary aim was to review molecular studies using microdialysis for the investigation of human chronic muscle pain, ie, chronic masticatory muscle pain, chronic trapezius myalgia, chronic whiplash-associated disorders, and chronic widespread pain/fibromyalgia syndrome. Several studies clearly showed elevated levels of serotonin, glutamate, lactate, and pyruvate in localized chronic myalgias and may be potential biomarkers. These results indicate that peripheral muscle alterations are parts of the activated pain mechanisms in common chronic pain conditions. Muscle alterations have been reported in fibromyalgia syndrome and chronic widespread pain, but more studies are needed before definite conclusions can be drawn. For other substances, results are inconclusive across studies and patient groups.

  • 9.
    Gerdle, Björn
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
    Larsson, Britt
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
    Forsberg, Frida
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
    Ghafouri, Nazdar
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
    Karlsson, Linn
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
    Stensson, Niclas
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Health Sciences.
    Ghafouri, Bijar
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center. Östergötlands Läns Landsting, Heart and Medicine Center, Occupational and Environmental Medicine Center.
    Chronic Widespread Pain: Increased Glutamate and Lactate Concentrations in the Trapezius Muscle and Plasma2014In: The Clinical Journal of Pain, ISSN 0749-8047, E-ISSN 1536-5409, Vol. 30, no 5, p. 409-420Article, review/survey (Refereed)
    Abstract [en]

    BACKGROUND:: Chronic widespread pain (CWP), including fibromyalgia syndrome (FM), is associated with prominent negative consequences. CWP has been associated with alterations in the central processing of nociception. Whereas some researchers consider CWP/FM as a central hyperexcitability pain condition, others suggest that the central alterations are maintained by peripheral nociceptive input. Microdialysis can be used in vivo to study muscle alterations in chronic myalgia. AIM:: The aim of the study was to investigate the plasma and interstitial concentrations of metabolites and algesics in the trapezius muscle of women with CWP and in pain-free women (CON).

    MATERIALS AND METHODS:: Seventeen women with CWP and 24 CON went through a clinical examination and completed a questionnaire; the pressure pain thresholds in the upper and lower extremities were registered. Microdialysis was conducted in the trapezius muscle, and a blood sample was drawn. Muscle blood flow, interstitial muscle concentrations, and plasma concentrations of lactate, pyruvate, glutamate, glucose, and glycerol (not in the plasma) were determined.

    RESULTS:: CWP patients had significantly increased interstitial muscle (P=0.02 to 0.001) and plasma (P=0.026 to 0.017) concentrations of lactate and glutamate. No significant differences existed in blood flow between CWP and CON. The interstitial concentrations-but not the plasma levels-of glutamate and lactate correlated significantly with aspects of pain such as pressure pain thresholds of the trapezius (R=0.22) and tibialis anterior (R=0.18) and the mean pain intensity (R=0.10) in CWP but not in CON.

    CONCLUSIONS:: The present study supports the suggestion that aspects of pain and central alterations in CWP/FM are influenced by peripheral tissue alterations.

  • 10.
    Ghafouri, Bijar
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Rehabilitation Medicine. Linköping University, Faculty of Health Sciences.
    Larsson, Britt
    Linköping University, Department of Clinical and Experimental Medicine, Rehabilitation Medicine. Linköping University, Faculty of Health Sciences.
    Sjörs, Anna
    Linköping University, Department of Clinical and Experimental Medicine, Rehabilitation Medicine. Linköping University, Faculty of Health Sciences.
    Leandersson, Per
    Linköping University, Department of Clinical and Experimental Medicine, Occupational and Environmental Medicine. Östergötlands Läns Landsting, Heart and Medicine Centre, Occupational and Environmental Medicine Centre. Linköping University, Faculty of Health Sciences.
    Gerdle, Björn
    Linköping University, Department of Clinical and Experimental Medicine, Rehabilitation Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Sinnescentrum, Pain and Rehabilitation Centre.
    Interstitial concentration of serotonin is increased in myalgic human trapezius muscle during rest, repetitive work and mental stress - an in vivo microdialysis study2010In: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686, Vol. 70, no 7, p. 478-486Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: The pathophysiology of trapezius myalgia is not fully elucidated. Serotonin (5-HT) is involved in modulation of nociception and hyperalgesia. Our aim was to compare the interstitial 5-HT levels of the trapezius muscle in women with chronic trapezius myalgia and in pain-free controls.

    MATERIALS AND METHODS: Microdialysate of the trapezius muscle collected every 20 minutes during rest, work (100 min) and stress (20 min) was used to study the dynamics of 5-HT in women with chronic trapezius myalgia (MYA; n=18) and in pain-free controls (CON; n=30).

    RESULTS: MYA had higher levels of 5-HT than CON at baseline, during repetitive work, during mental stress and during recovery. There were no significant time effects on 5-HT levels.

    CONCLUSION: 5-HT has the potential of a biomarker of chronic myalgia. Elevated levels of 5-HT may be involved in maintenance of habitual chronic pain and might contribute to increased pain during exercise by facilitating the effect of released algesic substances linked to such muscle demands.

  • 11.
    Ghafouri, Bijar
    et al.
    Linköping University, Department of Medical and Health Sciences, Rehabilitation Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center. Östergötlands Läns Landsting, Heart and Medicine Center, Occupational and Environmental Medicine Center.
    Persson, H Lennart
    Linköping University, Department of Medical and Health Sciences, Pulmonary Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Respiratory Medicine.
    Tagesson, Christer
    Linköping University, Department of Clinical and Experimental Medicine, Occupational and Environmental Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Occupational and Environmental Medicine Center.
    Intriguing bronchoalveolar lavage proteome in a case of pulmonary langerhans cell histiocytosis2013In: The American journal of case reports, ISSN 1941-5923, Vol. 14, p. 129-133Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Pulmonary Langerhans cell histiocytosis (PLCH) is a rare interstitial lung disease associated with tobacco smoke exposure. New insights into its pathogenesis and how it differs from that of chronic obstructive pulmonary disease (COPD) may be provided by proteomic studies on bronchoalveolar lavage fluid (BALF).

    CASE REPORT: We present the BALF proteome in a biopsy-proven case of PLCH and compare it with typical proteomes of COPD and of the healthy lung. The BALF proteins were separated by two-dimensional gel electrophoresis (2-DE) and the protein patterns were analyzed with a computerized 2-DE imaging system. As compared to the healthy subject and the COPD case, the PLCH case showed a strikingly different 2-DE pattern. There was much more IgG (heavy chain) and orosomucoid, and less α1-antitrypsin, surfactant protein-A, haptoglobin, cystatin-S, Clara cell protein 10, transthyretin and gelsolin. Moreover, no apolipoprotein-A1, pro-apolipoprotein-A1, amyloid P, calgranulin A, or calgranulin B was detected at all.

    CONCLUSIONS: This case of PLCH presents with an extreme BALF proteome lacking significant amounts of protective and anti-inflammatory proteins. Thus, the intriguing BALF proteome opens up new lines of research into the pathophysiology of PLCH and how its pathogenesis differs from that in COPD.

  • 12.
    Ghafouri, Nazdar
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center. Umeå University, Umeå, Sweden.
    Ghafouri, Bijar
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center. Östergötlands Läns Landsting, Heart and Medicine Center, Occupational and Environmental Medicine Center.
    Fowler, Christopher J.
    Umeå University, Sweden.
    Larsson, Britt
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
    Turkina, Maria
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Health Sciences.
    Karlsson, Linn
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
    Gerdle, Björn
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
    Effects of Two Different Specific Neck Exercise Interventions on Palmitoylethanolamide and Stearoylethanolamide Concentrations in the Interstitium of the Trapezius Muscle in Women with Chronic Neck Shoulder Pain2014In: Pain medicine (Malden, Mass.), ISSN 1526-2375, E-ISSN 1526-4637, Vol. 15, no 8, p. 1379-1389Article in journal (Refereed)
    Abstract [en]

    Purpose. Chronic neck/shoulder pain (CNSP) is one of the most common pain conditions. The understanding of mechanisms, including the peripheral balance between nociceptive and antinociceptive processes, is incomplete. N-acylethanolamines (NAEs) are a class of endogenous compounds that regulate inflammation and pain. The aim of this study was to investigate the levels of two NAEs: the peroxisome proliferator-activated receptor type-a ligand palmitoylethanolamide (PEA) and stearoylethanolamide (SEA) in the muscle interstitium of the trapezius muscle in women with CNSP randomized to two different neck specific training programs and in a healthy pain-free control group (CON). Materials and Methods. Fifty-seven women with CNSP were randomized to strength + stretch or stretch alone exercise programs. Twenty-nine subjects underwent microdialysis procedure before and after 4-6 months of exercise. Twenty-four CON subjects underwent microdialysis procedure before and after 4-6 months without any intervention in between. Microdialysate samples were collected from the trapezius muscle and analyzed by mass spectrometry for PEA and SEA levels. Results. PEA and SEA levels were significantly higher in CNSP patients compared with CON. PEA was significantly higher in CNSP than in CON after both training programs. SEA was significantly higher in CNSP than in CON after stretch alone but not after strength + stretch training. A significant positive correlation was found between changes in pain intensity and in SEA levels in the strength + stretch group, but not in the stretch alone group. Conclusion. Our results indicate that exercise interventions differentially affect the levels of the bioactive lipids PEA and SEA in the interstitium of the trapezius muscle in women with CNSP.

  • 13.
    Ghafouri, Nazdar
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Health Sciences.
    Ghafouri, Bijar
    Linköping University, Department of Medical and Health Sciences, Rehabilitation Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center. Östergötlands Läns Landsting, Heart and Medicine Center, Occupational and Environmental Medicine Center.
    Larsson, Britt
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
    Stensson, Niclas
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Health Sciences.
    Fowler, Christopher J.
    Umeå University, Sweden .
    Gerdle, Björn
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
    Palmitoylethanolamide and stearoylethanolamide levels in the interstitium of the trapezius muscle of women with chronic widespread pain and chronic neck-shoulder pain correlate with pain intensity and sensitivity2013In: Pain, ISSN 0304-3959, E-ISSN 1872-6623, Vol. 154, no 9, p. 1649-1658Article in journal (Refereed)
    Abstract [en]

    Chronic widespread pain (CWP) is a complex condition characterized by central hyperexcitability and altered descending control of nociception. However, nociceptive input from deep tissues is suggested to be an important drive. N-Acylethanolamines (NAEs) are endogenous lipid mediators involved in regulation of inflammation and pain. Previously we have reported elevated levels of the 2 NAEs, the peroxisome proliferator-activated receptor type-alpha ligand N-palmitoylethanolamine (PEA) and N-stearoylethanolamine (SEA) in chronic neck/shoulder pain (CNSP). In the present study, the levels of PEA and SEA in women with CWP (n = 18), CNSP (n = 34) and healthy controls (CON, n = 24) were investigated. All subjects went through clinical examination, pressure pain threshold measurements and induction of experimental pain in the tibialis anterior muscle. Microdialysis dialysate of the trapezius was collected before and after subjects performed a repetitive low-force exercise and analyzed by mass spectrometry. The levels of PEA and SEA in CNSP were significantly higher post exercise compared with CWP, and both pre and post exercise compared with CON. Levels of both NAEs decreased significantly pre to post exercise in CWP. Intercorrelations existed between aspects of pain intensity and sensitivity and the level of the 2 NAEs in CWP and CNSP. This is the first study demonstrating that CNSP and CWP differ in levels of NAEs in response to a low-force exercise which induces pain. Increases in pain intensity as a consequence of low-force exercise were associated with low levels of PEA and SEA in CNSP and CWP. These results indicate that PEA and SEA have antinociceptive roles in humans.

  • 14.
    Ghafouri, Nazdar
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Rehabilitation Medicine. Linköping University, Faculty of Health Sciences.
    Ghafouri, Bijar
    Linköping University, Department of Clinical and Experimental Medicine, Rehabilitation Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Sinnescentrum, Pain and Rehabilitation Centre. Östergötlands Läns Landsting, Heart and Medicine Centre, Occupational and Environmental Medicine Centre.
    Larsson, Britt
    Linköping University, Department of Clinical and Experimental Medicine, Rehabilitation Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Sinnescentrum, Pain and Rehabilitation Centre.
    Turkina, Maria
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
    Karlsson, Linn
    Linköping University, Department of Clinical and Experimental Medicine, Rehabilitation Medicine. Linköping University, Faculty of Health Sciences.
    Fowler, Christopher J.
    Östergötlands Läns Landsting, Sinnescentrum, Pain and Rehabilitation Centre.
    Gerdle, Björn
    Linköping University, Department of Clinical and Experimental Medicine, Rehabilitation Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Sinnescentrum, Pain and Rehabilitation Centre.
    High Levels of N-Palmitoylethanolamide and N-Stearoylethanolamide in Microdialysate Samples from Myalgic Trapezius Muscle in Women2011In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 6, no 11Article in journal (Refereed)
    Abstract [en]

    Background: N-acylethanolamines (NAEs) are endogenous compounds that regulate inflammation and pain. These include the cannabinoid ligand anandamide (AEA) and the peroxisome proliferator-activated receptor-a ligand palmitoylethanolamide (PEA). Little is known as to the levels of NAEs in pain states in human, particularly in the skeletal muscle. The aim of this study was to investigate the levels of these lipid mediators in muscle dialysate from women with chronic neck-/shoulder pain compared to healthy controls. Methods: Eleven women with chronic neck-/shoulder pain and eleven healthy women participated in this study. All participants went through microdialysis procedures in the trapezius muscle. Muscle dialysate samples were collected during four hours and analysed by nano liquid chromatography tandem mass spectrometry (nLC-MS/MS). Results: We were able to detect AEA, PEA, N-stearoylethanolamine (SEA) and 2-arachidonoylglycerol (2-AG) in a single chromatographic run. Of the NAEs studied, PEA and SEA were clearly detectable in the muscle microdialysate samples. The muscle dialysate levels of PEA and SEA were significantly higher in myalgic subjects compared to healthy controls. Conclusion: This study demonstrates that microdialysis in combination with mass spectrometry can be used for analysing NAEs in human muscle tissue regularly over time. Furthermore the significant group differences in the concentration of PEA and SEA in this study might fill an important gap in our knowledge of mechanisms in chronic myalgia in humans. In the long run this expanded understanding of nociceptive and anitinociceptive processes in the muscle may provide a base for ameliorating treatment and rehabilitation of pain.

  • 15.
    Graff, Pål
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Occupational and Environmental Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Occupational and Environmental Medicine Center.
    Fredrikson, Mats
    Linköping University, Department of Clinical and Experimental Medicine, Occupational and Environmental Medicine. Linköping University, Faculty of Health Sciences.
    Jönsson, Pia
    Linköping University, Department of Clinical and Experimental Medicine, Occupational and Environmental Medicine. Linköping University, Faculty of Health Sciences.
    Flodin, Ulf
    Linköping University, Department of Clinical and Experimental Medicine, Occupational and Environmental Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Occupational and Environmental Medicine Center.
    Non-sensitising air pollution at workplaces and adult-onset asthma in the beginning of this millennium2011In: International Archives of Occupational and Environmental Health, ISSN 0340-0131, E-ISSN 1432-1246, Vol. 84, no 7, p. 797-804Article in journal (Refereed)
    Abstract [en]

    Purpose: This case-control study was undertaken to elucidate the controversy concerning whether low-level, long-term exposure to non-sensitising air pollution at workplaces may cause asthma. Methods: A case-control study of 192 adult-onset asthma cases aged 20-65 years and 323 controls was conducted in the southeast of Sweden. Cases were identified from computerised registers from the region, diagnosed 2000-2004 and diagnoses were confirmed via medical files. Referents were randomised from the population register of the region. Exposure was monitored by a 16-page questionnaire. Special attention was devoted to identifying and in the final analyses excluding subjects exposed to sensitising agents. Results: Three years or more of occupational exposure to air pollution from dust, smoke, fumes or vapours before the year of diagnosis by analyses adjusting for age yielded an increased risk for asthma (OR = 2.3, 95% CI 1.2-4.2) in men, while in women, no risk was seen. In a multiple logistic regression analysis in men without allergy in childhood, a significant risk was seen (OR = 2.8, 95% CI 1.07-7.4), when subjects exposed to identified allergens were excluded. In women, no excess risk was observed from occupational air pollution. Conclusion: The results of this study support an association between occupational exposure to low level non-sensitising air pollution and adult-onset asthma in men.

  • 16.
    Hadrevi, J
    et al.
    Umeå University, Sweden .
    Ghafouri, Bijar
    Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center. Östergötlands Läns Landsting, Heart and Medicine Center, Occupational and Environmental Medicine Center. Linköping University, Department of Medical and Health Sciences, Division of Community Medicine.
    Sjörs, Anna
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Health Sciences.
    Antti, H
    Umeå University, Sweden .
    Larsson, Britt
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
    Crenshaw, A G.
    University of Gavle, Sweden .
    Gerdle, Björn
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
    Hellstrom, F
    University of Gavle, Sweden .
    Comparative metabolomics of muscle interstitium fluid in human trapezius myalgia: an in vivo microdialysis study2013In: European Journal of Applied Physiology, ISSN 1439-6319, E-ISSN 1439-6327, Vol. 113, no 12, p. 2977-2989Article in journal (Refereed)
    Abstract [en]

    The mechanisms behind trapezius myalgia are unclear. Many hypotheses have been presented suggesting an altered metabolism in the muscle. Here, muscle microdialysate from healthy and myalgic muscle is analysed using metabolomics. Metabolomics analyse a vast number of metabolites, enabling a comprehensive explorative screening of the cellular processes in the muscle. less thanbrgreater than less thanbrgreater thanMicrodialysate samples were obtained from the shoulder muscle of healthy and myalgic subjects that performed a work and stress test. Samples from the baseline period and from the recovery period were analysed using gas chromatography-mass spectrometry (GC-MS) together with multivariate analysis to detect differences in extracellular content of metabolites between groups. Systematic differences in metabolites between groups were identified using multivariate analysis and orthogonal partial least square discriminate analysis (OPLS-DA). A complementary Mann-Whitney U test of group difference in individual metabolites was also performed. less thanbrgreater than less thanbrgreater thanA large number of metabolites were detected and identified in this screening study. At baseline, no systematic differences between groups were observed according to the OPLS-DA. However, two metabolites, l-leucine and pyroglutamic acid, were significantly more abundant in the myalgic muscle compared to the healthy muscle. In the recovery period, systematic difference in metabolites between the groups was observed according to the OPLS-DA. The groups differed in amino acids, fatty acids and carbohydrates. Myristic acid and putrescine were significantly more abundant and beta-d-glucopyranose was significantly less abundant in the myalgic muscle. less thanbrgreater than less thanbrgreater thanThis study provides important information regarding the metabolite content, thereby presenting new clues regarding the pathophysiology of the myalgic muscle.

  • 17.
    Hadrevi, Jenny
    et al.
    Umeå University, Sweden.
    Ghafouri, Bijar
    Linköping University, Department of Medical and Health Sciences, Rehabilitation Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center. Östergötlands Läns Landsting, Heart and Medicine Center, Occupational and Environmental Medicine Center.
    Larsson, Britt
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
    Gerdle, Björn
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
    Hellstrom, Fredrik
    University of Gävle, Sweden.
    Multivariate Modeling of Proteins Related to Trapezius Myalgia, a Comparative Study of Female Cleaners with or without Pain2013In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 8, no 9Article in journal (Refereed)
    Abstract [en]

    The prevalence of chronic trapezius myalgia is high in women with high exposure to awkward working positions, repetitive movements and movements with high precision demands. The mechanisms behind chronic trapezius myalgia are not fully understood. The purpose of this study was to explore the differences in protein content between healthy and myalgic trapezius muscle using proteomics. Muscle biopsies from 12 female cleaners with work-related trapezius myalgia and 12 pain free female cleaners were obtained from the descending part of the trapezius. Proteins were separated with two-dimensional differential gel electrophoresis (2D-DIGE) and selected proteins were identified with mass spectrometry. In order to discriminate the two groups, quantified proteins were fitted to a multivariate analysis: partial least square discriminate analysis. The model separated 28 unique proteins which were related to glycolysis, the tricaboxylic acid cycle, to the contractile apparatus, the cytoskeleton and to acute response proteins. The results suggest altered metabolism, a higher abundance of proteins related to inflammation in myalgic cleaners compared to healthy, and a possible alteration of the contractile apparatus. This explorative proteomic screening of proteins related to chronic pain in the trapezius muscle provides new important aspects of the pathophysiology behind chronic trapezius myalgia.

  • 18.
    Han, Y.
    et al.
    First Affiliated Hospital, Shenyang.
    Wang, Y.
    First Affiliated Hospital, Shenyang.
    Xu, H.-T.
    First Affiliated Hospital, Shenyang.
    Yang, L.-H.
    First Affiliated Hospital, Shenyang.
    Wei, Q.
    First Affiliated Hospital, Shenyang.
    Liu, Y.
    First Affiliated Hospital, Shenyang.
    Zhang, Y.
    First Affiliated Hospital, Shenyang.
    Zhao, Y.
    First Affiliated Hospital, Shenyang.
    Dai, S.-D.
    First Affiliated Hospital, Shenyang.
    Miao, Y.
    First Affiliated Hospital, Shenyang.
    Yu, J.-H.
    First Affiliated Hospital, Shenyang.
    Zhang, J.-Y.
    First Affiliated Hospital, Shenyang.
    Li, G.
    First Affiliated Hospital, Shenyang.
    Yuan, Ximing
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Occupational and Environmental Medicine Centre.
    Wang, E.-H.
    First Affiliated Hospital, Shenyang.
    X-Radiation Induces Non-Small-Cell Lung Cancer Apoptosis by Upregulation of Axin Expression2009In: International Journal of Radiation Oncology Biology Physics, ISSN 0360-3016, Vol. 75, no 2, p. 518-526Article in journal (Refereed)
    Abstract [en]

    Purpose: Axis inhibition (Axin) is an important negative regulator of the Wnt pathway. This study investigated the relationship between Axin expression and sensitivity to X-rays in non-small-cell lung cancer (NSCLC) to find a useful indicator of radiosensitivity. Methods and Materials: Tissue from NSCLC patients, A549 cells, and BE1 cells expressing Axin were exposed to 1-Gy of X-radiation. Axin and p53 expression levels were detected by immunohistochemistry and reverse transcription-PCR. Apoptosis was determined by TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling) assay and FACS (fluorescence-activate cell sorter) analysis. Caspase-3 activity was determined by Western blotting. Phospho-JNK expression was determined by immunofluorescence. Results: The expression of Axin was significantly lower in NSCLC tissues than in normal lung tissues (p less than 0.05). Axin expression correlates with differentiation, TNM staging, and lymph node metastasis of NSCLC (p less than 0.05). Its expression negatively correlates with the expression of p53(mt) (p=0.000) and positively correlates with apoptosis (p=0.002). The prognosis of patients with high expression of Axin was better than those with low expression. X-radiation increases Axin expression in NSCLC tissue, and caspase-3 is significantly higher in samples in which Axin is increased (p less than 0.05). Both X-radiation and Axin induce apoptosis of A549 and BE1 cells; however, the combination of the two enhances the apoptotic effect (p less than 0.05). In A549 cells, inhibition of p53 blocks Axin-induced apoptosis, whereas in BE1 cells, the JNK pathway is required. Conclusions: Axin induces the p53 apoptotic pathway in cells where this pathway is intact; however, in cells expressing p53(mt), Axin induces apoptosis via the JNK pathway. Elevated Axin expression following X-ray exposure is a reliable indicator for determining the radiosensitivity of NSCLC.

  • 19.
    Han, Yang
    et al.
    College of Basic Medical Sciences, First Affiliated Hospital of China Medical University, Shenyang, China.
    Zhang, Yong
    College of Basic Medical Sciences, First Affiliated Hospital of China Medical University, Shenyang, China.
    Yang, Lian-he
    College of Basic Medical Sciences, First Affiliated Hospital of China Medical University, Shenyang, China.
    Mi, Xiao-yi
    College of Basic Medical Sciences, First Affiliated Hospital of China Medical University, Shenyang, China.
    Dai, Shun-dong
    College of Basic Medical Sciences, First Affiliated Hospital of China Medical University, Shenyang, China.
    Li, Qing-chang
    College of Basic Medical Sciences, First Affiliated Hospital of China Medical University, Shenyang, China.
    Xu, Hong-tao
    College of Basic Medical Sciences, First Affiliated Hospital of China Medical University, Shenyang, China.
    Yu, Juan-han
    College of Basic Medical Sciences, First Affiliated Hospital of China Medical University, Shenyang, China.
    Li, Guang
    First Affiliated Hospital of China Medical University, Shenyang, China.
    Zhao, Jing
    First Affiliated Hospital of China Medical University, Shenyang, China.
    Han, Chong
    First Affiliated Hospital of China Medical University, Shenyang, China.
    Yuan, Xi-ming
    Linköping University, Department of Clinical and Experimental Medicine, Experimental Pathology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Occupational and Environmental Medicine Centre.
    Wang, En-hua
    College of Basic Medical Sciences, First Affiliated Hospital of China Medical University, Shenyang, China.
    X-radiation inhibits histone deacetylase 1 and 2, upregulates Axin expression and induces apoptosis in non-small cell lung cancer2012In: Radiation Oncology, ISSN 1748-717X, E-ISSN 1748-717X, Vol. 7, no 183Article in journal (Refereed)
    Abstract [en]

    Background

    Histone deacetylase (HDAC) plays an important role in the deacetylation of histone, which can alter gene expression patterns and affect cell behavior associated with malignant transformation. The aims of this study were to investigate the relationships between HDAC1, HDAC2, clinicopathologic characteristics, patient prognosis and apoptosis, to clarify the mechanism of upregulation of the Axis inhibitor Axin (an important regulator of the Wnt pathway) by X-radiation and to elucidate the effect of siRNA on radiation therapy of non-small cell lung cancer (NSCLC).

    Methods

    HDAC1 and HDAC2 expression levels were measured by immunohistochemistry and reverse transcription PCR. Apoptosis was determined by terminal deoxynucleotidyl transferase-mediated dUTP-nick end labeling and fluorescence activated cell sorting. BE1 cells expressing Axin were exposed to 2 Gy of X-radiation.

    Results

    Expression of HDAC1 and that of HDAC2 were correlated, and significantly higher in NSCLC tissues than in normal lung tissues (P < 0.05). HDAC1 and HDAC2 expression was correlated with pTNM stage and negatively correlated with differentiation of NSCLC and apoptotic index (P < 0.05). The prognosis of patients with low expression of HDAC1 and HDAC2 was better than that of those with high expression. X-radiation and siRNA inhibited HDAC1 and HDAC2 expression in NSCLC cells and Axin levels were significantly higher in BE1 cells.

    Conclusions

    X-radiation and siRNA inhibit expression of HDAC1 and HDAC2, weaken the inhibitory effect of HDAC on Axin, upregulate Axin expression and induce apoptosis of lung cancer cells. Inhibition of HDAC1 and HDAC2 is a means of enhancing the radiosensitivity of NSCLC.

  • 20.
    Helmfrid, Ingela
    et al.
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Occupational and Environmental Medicine Centre.
    Berglund, Marika
    Karolinska Institutet, Stockholm, Sweden.
    Lofman, Owe
    Norwegian University of Life Sciences, Ås, Norway.
    Wingren, Gun
    Linköping University, Department of Clinical and Experimental Medicine, Work and Environmental Science. Linköping University, Faculty of Health Sciences.
    Health effects and exposure to polychlorinated biphenyls (PCBs) and metals in a contaminated community2012In: Environment International, ISSN 0160-4120, E-ISSN 1873-6750, Vol. 44, p. 53-58Article in journal (Refereed)
    Abstract [en]

    Environmental measurements carried out by local authorities during the 1970s, 80s and 90s in an area contaminated by hundreds of years of industrial activities have revealed high levels of zinc (Zn), copper (Cu), lead (Pb) and cadmium (Cd) in soil, vegetables, root crops, berries and mushrooms. In 1972, a large quantity of oil contaminated with polychlorinated biphenyls (PCBs) was accidentally spilled into the river running through the village. To investigate the possible health effects of exposure from local sources, all cancer diagnoses, registered in 1960-2003 for individuals living in the study area, were collected from the regional cancer register of southeast Sweden. The total cancer incidence was non-significantly decreased both among males and females as compared to national rates (SIR = 0.91) for each gender. Among males, increased risks, of border-line significance, were seen for testicular cancer and lymphomas as well as significantly decreased risks for cancer in the rectum, respiratory system and brain. Information on lifetime residence, occupation, smoking habits, diseases, childbirth and food consumption, was collected via questionnaires from cancer cases and randomly selected controls. In both genders combined, significant associations were found for total cancer and high consumption of local perch, and for lymphomas and high consumption of both perch and pikeperch. Female breast cancer was significantly associated with high consumption of local perch and pike as well as with work in metal production. Mothers residing in the parish before the age of five reported significantly more preterm child deliveries. In spite of study limitations, the results indicate that residing in a rural contaminated area may contribute to the development of certain cancers and reproductive effects. In females, high consumption of local fish was shown to be the strongest determinant for total cancer, while in males, the strongest determinant was residing in the study area the first five years of life. Further research including validation of exposure using biomarkers is required to verify the findings as well as future studies in other polluted areas in Sweden with larger population bases.

  • 21.
    Holleboom, Adriaan G
    et al.
    Department of Vascular Medicine, Academic Medical Center, Amsterdam 1105AZ, The Netherlands.
    Karlsson, Helen
    Linköping University, Department of Clinical and Experimental Medicine, Occupational and Environmental Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Occupational and Environmental Medicine Centre.
    Lin, Ruei-Shiuan
    Section on Biological Chemistry, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 20892, USA.
    Beres, Thomas M
    Section on Biological Chemistry, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 20892, USA.
    Sierts, Jeroen A
    Department of Experimental Vascular Medicine, Academic Medical Center, Amsterdam 1105AZ, The Netherlands.
    Herman, Daniel S
    Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.
    Stroes, Erik S G
    Department of Vascular Medicine, Academic Medical Center, Amsterdam 1105AZ, The Netherlands.
    Aerts, Johannes M
    Department of Medical Biochemistry, Academic Medical Center, Amsterdam 1105AZ, The Netherlands.
    Kastelein, John J P
    Department of Vascular Medicine, Academic Medical Center, Amsterdam 1105AZ, The Netherlands.
    Motazacker, Mohammad M
    Department of Experimental Vascular Medicine, Academic Medical Center, Amsterdam 1105AZ, The Netherlands.
    Dallinga-Thie, Geesje M
    Department of Vascular Medicine, Academic Medical Center, Amsterdam 1105AZ, The Netherlands.
    Levels, Johannes H M
    Department of Experimental Vascular Medicine, Academic Medical Center, Amsterdam 1105AZ, The Netherlands.
    Zwinderman, Aeilko H
    Department of Clinical Epidemiology, Biostatistics, and Bioinformatics, Academic Medical Center, Amsterdam 1105AZ, The Netherlands.
    Seidman, Jonathan G
    Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.
    Seidman, Christine E
    Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.
    Ljunggren, Stefan
    Linköping University, Department of Clinical and Experimental Medicine, Occupational and Environmental Medicine. Linköping University, Faculty of Health Sciences.
    Lefeber, Dirk J
    Department of Neurology, Radboud University Nijmegen Medical Center, Nijmegen 6525GA, The Netherlands.
    Morava, Eva
    Institute for Genetic and Metabolic Disease, Radboud University Nijmegen Medical Center, Nijmegen 6525GA, The Netherlands.
    Wevers, Ron A
    Department of Laboratory Medicine, Radboud University Nijmegen Medical Center, Nijmegen 6525GA, The Netherlands.
    Fritz, Timothy A
    Food and Drug Administration, Rockville, MD 20852, USA.
    Tabak, Lawrence A
    Section on Biological Chemistry, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 20892, USA.
    Lindahl, Mats
    Linköping University, Department of Clinical and Experimental Medicine, Occupational and Environmental Medicine. Linköping University, Faculty of Health Sciences.
    Hovingh, G Kees
    Department of Vascular Medicine, Academic Medical Center, Amsterdam 1105AZ, The Netherlands.
    Kuivenhoven, Jan Albert
    Department of Experimental Vascular Medicine, Academic Medical Center, Amsterdam 1105AZ, The Netherlands.
    Heterozygosity for a Loss-of-Function Mutation in GALNT2 Improves Plasma Triglyceride Clearance in Man2011In: Cell Metabolism, ISSN 1550-4131, E-ISSN 1932-7420, Vol. 14, no 6, p. 811-8Article in journal (Refereed)
    Abstract [en]

    Genome-wide association studies have identified GALNT2 as a candidate gene in lipid metabolism, but it is not known how the encoded enzyme ppGalNAc-T2, which contributes to the initiation of mucin-type O-linked glycosylation, mediates this effect. In two probands with elevated plasma high-density lipoprotein cholesterol and reduced triglycerides, we identified a mutation in GALNT2. It is shown that carriers have improved postprandial triglyceride clearance, which is likely attributable to attenuated glycosylation of apolipoprotein (apo) C-III, as observed in their plasma. This protein inhibits lipoprotein lipase (LPL), which hydrolyses plasma triglycerides. We show that an apoC-III-based peptide is a substrate for ppGalNAc-T2 while its glycosylation by the mutant enzyme is impaired. In addition, neuraminidase treatment of apoC-III which removes the sialic acids from its glycan chain decreases its potential to inhibit LPL. Combined, these data suggest that ppGalNAc-T2 can affect lipid metabolism through apoC-III glycosylation, thereby establishing GALNT2 as a lipid-modifying gene.

  • 22.
    Irander, Kristina
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Borres, M.P.
    Uppsala University, Sweden Thermo Fisher Science, Sweden .
    Ghafouri, Bijar
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center. Östergötlands Läns Landsting, Heart and Medicine Center, Occupational and Environmental Medicine Center.
    The effects of physical exercise and smoking habits on the expression of SPLUNC1 in nasal lavage fluids from allergic rhinitis subjects2014In: International Journal of Pediatric Otorhinolaryngology, ISSN 0165-5876, E-ISSN 1872-8464, Vol. 78, no 4, p. 618-622Article in journal (Refereed)
    Abstract [en]

    Objective: Palate lung nasal epithelial clone (PLUNC) is a family of proteins, which are proposed to participate in the innate immune defense against infections in the upper aero-digestive tract. The aim of this study was to investigate the expression of SPLUNC1 in allergic rhinitis subjects with considerations taken to the mucosa( function and smoking habits. Methods: The participants, recruited from a cohort followed from infancy, were re-examined at the age of 18 years regarding allergy development. Based on medical histories and skin prick tests the participants were classified into groups with persistent allergic rhinitis (n = 18), intermittent allergic rhinitis (n = 8) and healthy controls (n = 13). Seven subjects (3, 2 and 2 in each group, respectively) reported smoking habits. The SPLUNC1 levels in nasal lavage fluids were analyzed by Western blot. Changes in the volume of the proper nasal cavity before and after physical exercise (Vol2(increase)) were analyzed by acoustic rhinometiy. Results: Compared to the control group the SPLUNC1 level was significantly lower in the persistent allergy group (3.8 +/- 3.4 OD vs. 1.3 +/- 1.5 OD; p = 0.02), but not in the intermittent allergy group without current exposure to allergens (3.6 +/- 4.7 OD). No differences were found in Vol2(increase) between any of the allergy groups and controls. In smokers Vol2(increase) was significantly reduced (p less than 0.01) and the SPLUNC1 levels were lower compared to non-smokers. A significant correlation was found between SPLUNC1 and vol2(increase) (pless than0.01; r = 0.53) in non-smokers. Conclusions: Current allergen exposure has an impact on SPLUNC1 expression in nasal lavage fluid, why allergy ought to be considered in study populations where analyses of SPLUNC1 levels are included in the reports. The normal nasal decongestion after exercise was not affected by allergy in contrast to smoking habits. The correlation between SPLUNC1 levels and Vol2(increase) in non-smokers may indicate involvement of SPLUNC1 in the regulation of the normal function of the nasal mucosa. Complementary studies are needed to confirm the smoke-related reduction of SPLUNC1 expression and to analyze the possible participation of SPLUNC1 in the nasal mucosa regulation.

  • 23.
    Irander, Kristina
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Palm, Jörgen P.
    Karolinska Institutet, Sweden .
    Borres, Magnus P.
    Sahlgrenska Academy of Göteborg University, Sweden .
    Ghafouri, Bijar
    Linköping University, Department of Medical and Health Sciences, Rehabilitation Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center. Östergötlands Läns Landsting, Heart and Medicine Center, Occupational and Environmental Medicine Center.
    Clara cell protein in nasal lavage fluid and nasalnitric oxide - biomarkers with anti-inflammatoryproperties in allergic rhinitis2012In: Clinical and Molecular Allergy, ISSN 1476-7961, E-ISSN 1476-7961, Vol. 10, no 4Article in journal (Refereed)
    Abstract [en]

    Background

    Clara cell protein (CC16) is ascribed a protective and anti-inflammatory role in airway         inflammation. Lower levels have been observed in asthmatic subjects as well as in         subjects with intermittent allergic rhinitis than in healthy controls. Nasal nitric         oxide (nNO) is present in high concentrations in the upper airways, and considered         a biomarker with beneficial effects, due to inhibition of bacteria and viruses along         with stimulation of ciliary motility. The aim of this study was to evaluate the presumed         anti-inflammatory effects of nasal CC16 and nNO in subjects with allergic rhinitis.     

    Methods

    The levels of CC16 in nasal lavage fluids, achieved from subjects with persistent         allergic rhinitis (n = 13), intermittent allergic rhinitis in an allergen free interval         (n = 5) and healthy controls (n = 7), were analyzed by Western blot. The levels of         nNO were measured by the subtraction method using NIOX®. The occurrences of effector cells in allergic inflammation, i.e. metachromatic cells         (MC, mast cells and basophiles) and eosinophils (Eos) were analyzed by light microscopy         in samples achieved by nasal brushing.     

    Results

    The levels of CC16 correlated with nNO levels (r2 = 0.37; p = 0.02) in allergic subjects.     

    The levels of both biomarkers showed inverse relationships with MC occurrence, as         higher levels of CC16 (p = 0.03) and nNO (p = 0.05) were found in allergic subjects         with no demonstrable MC compared to the levels in subjects with demonstrable MC. Similar         relationships, but not reaching significance, were observed between the CC16 and nNO         levels and Eos occurrence. The levels of CC16 and nNO did not differ between the allergic         and the control groups.     

    Conclusions

    The correlation between nasal CC16 and nNO levels in patients with allergic rhinitis,         along with an inverse relationship between their levels and the occurrences of MC         in allergic inflammation, may indicate that both biomarkers have anti-inflammatory         effects by suppression of cell recruitment. The mechanisms behind these observations         warrant further analyses.

  • 24.
    Karlsson, Helen
    et al.
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Occupational and Environmental Medicine Center.
    Chroni, Angeliki
    Institute of Biology, National Center for Scientific Research, Demokritos, Athens, Greece.
    George, Leondaritis
    Institute of Biology, National Center for Scientific Research, Demokritos, Athens, Greece.
    Lipids and Lipoproteins in Atherosclerosis / Special issue2011In: Journal of Lipids, ISSN 2090-3030, E-ISSN 2090-3049Article in journal (Refereed)
    Abstract [en]

    Atherosclerosis is a focal disease of the arterial wall that leads to cardiovascular disease (CVD), the biggest cause of morbidity and mortality in Western societies. Atherosclerosis is a complex, chronic, progressive disease that affects large and medium-sized arteries. Atherosclerotic lesions are promoted by low-density lipoproteins and form from accumulation of fatty substances, cholesterol, cellular waste products, calcium, and fibrin in the inner lining of the arterial wall. Lipoproteins are complexes of amphipathic proteins with lipids at variable ratios, densities, and sizes. Their role is to transport water-insoluble lipids in the blood. Plasma lipoproteins have traditionally been grouped into five major classes, based on their buoyant density: chylomicrons, very low-density lipoproteins (VLDL), intermediate-density lipoproteins (IDL), low-density lipoproteins (LDL), and high-density lipoproteins (HDL). It is believed that atherogenic lipoproteins, such as LDL and lipoprotein remnants, that float in the VLDL IDL region, promote atherosclerosis, and antiatherogenic lipoproteins, such as HDL, protect from atherosclerosis. Despite many advances in cardiology, atherosclerosis remains an important medical problem suggesting that some steps in pathogenic mechanisms remain unclear.

    This special issue contains a series of reviews and original research articles that seek to provide insight into the role of lipids and lipoproteins in health and disease with emphasis given on their implication in atherosclerosis.

  • 25.
    Karlsson, Helen
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Occupational and Environmental Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Occupational and Environmental Medicine Center.
    Lindbom, John
    Linköping University, Department of Clinical and Experimental Medicine, Occupational and Environmental Medicine. Linköping University, Faculty of Health Sciences.
    Ghafouri, Bijar
    Linköping University, Department of Clinical and Experimental Medicine, Occupational and Environmental Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center. Östergötlands Läns Landsting, Heart and Medicine Center, Occupational and Environmental Medicine Center.
    Lindahl, Mats
    Linköping University, Department of Clinical and Experimental Medicine, Occupational and Environmental Medicine. Linköping University, Faculty of Health Sciences.
    Tagesson, Christer
    Linköping University, Department of Clinical and Experimental Medicine, Occupational and Environmental Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Occupational and Environmental Medicine Center.
    Gustafsson, Mats
    Östergötlands Läns Landsting, Heart and Medicine Center, Occupational and Environmental Medicine Center.
    Ljungman, Anders G
    Linköping University, Department of Clinical and Experimental Medicine, Occupational and Environmental Medicine. Linköping University, Faculty of Health Sciences.
    Wear Particles from Studded Tires and Granite Pavement Induce Pro-inflammatory Alterations in Human Monocyte-Derived Macrophages: A Proteomic Study.2011In: Chemical Research in Toxicology, ISSN 0893-228X, E-ISSN 1520-5010, Vol. 24, p. 45-53Article in journal (Refereed)
    Abstract [en]

    Airborne particulate matter is considered to be one of the environmental contributors to the mortality in cancer, respiratory, and cardiovascular diseases. For future preventive actions, it is of major concern to investigate the toxicity of defined groups of airborne particles and to clarify their pathways in biological tissues. To expand the knowledge beyond general inflammatory markers, this study examined the toxicoproteomic effects on human monocyte derived macrophages after exposure to wear particles generated from the interface of studded tires and a granite-containing pavement. As comparison, the effect of endotoxin was also investigated. The macrophage proteome was separated using two-dimensional gel electrophoresis. Detected proteins were quantified, and selected proteins were identified by matrix-assisted laser desorption/ionization time of flight mass spectrometry. Among analyzed proteins, seven were significantly decreased and three were increased by exposure to wear particles as compared to unexposed control cells. Endotoxin exposure resulted in significant changes in the expression of six proteins: four decreased and two increased. For example, macrophage capping protein was significantly increased after wear particle exposure only, whereas calgizzarin and galectin-3 were increased by both wear particle and endotoxin exposure. Overall, proteins associated with inflammatory response were increased and proteins involved in cellular functions such as redox balance, anti-inflammatory response, and glycolysis were decreased. Investigating the effects of characterized wear particles on human macrophages with a toxicoproteomic approach has shown to be useful in the search for more detailed information about specific pathways and possible biological markers.

  • 26.
    Karlsson, Helen
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Work and Environmental Science. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Occupational and Environmental Medicine Center.
    Ljunggren, Stefan
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Ahrén, Maria
    Linköping University, Department of Physics, Chemistry and Biology, Molecular Surface Physics and Nano Science. Linköping University, Faculty of Science & Engineering.
    Ghafouri, Bijar
    Linköping University, Department of Medical and Health Sciences, Rehabilitation Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
    Uvdal, Kajsa
    Linköping University, Department of Physics, Chemistry and Biology, Molecular Surface Physics and Nano Science. Linköping University, Faculty of Science & Engineering.
    Lindahl, Mats
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Ljungman, Anders
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Two-dimensional gel electrophoresis and mass spectrometry in studies of nanoparticle-protein interactions2012In: Gel electrophoresis-Advanced Techniques / [ed] Sameh Magdeldin, Rijeka, Croatia: In Tech , 2012, p. 1-32Chapter in book (Other academic)
    Abstract [en]

    Over the years a number of epidemiological studies have shown that PM from combustion sources such as motor vehicles contributes to respiratory and cardiovascular morbidity and mortality.Especially so do the ultra-fine particles (UFPs) with a diameter less than 0.1 micrometer.UFPs from combustion engines are capable to translocate over the alveolar–capillary barrier.  When nano-sized PM (nanoparticles, NP), which are small enough to enter the blood stream, do so they are likely to interact with plasma proteins and this protein-NP interaction will probably affect the fate of and the effects caused by the NPs in the human body. Here, by using a proteomic approach, we present results showing that several proteins indeed are associated to NPs that have in vitro been introduced to human blood plasma.

  • 27.
    Karlsson, Helen
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Occupational and Environmental Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Occupational and Environmental Medicine Centre. Östergötlands Läns Landsting.
    Sundberg, Sofie
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Levels, J H M
    Acad Med Centre, Amsterdam, Netherlands .
    Turkina, Maria
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
    Daniel, G
    National Centre for Science Research Demokritos.
    Chroni, A
    National Centre for Science Research Demokritos.
    Kuivenhoven, J A
    Acad Med Centre, Amsterdam, Netherlands .
    Hovingh, G K
    Acad Med Centre, Amsterdam, Netherlands.
    Holleboom, A G
    Acad Med Centre, Amsterdam, Netherlands.
    Lindahl, Mats
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    MUTANT apo A-I (L178P) IDENTIFIED IN HDL FROM HETEROZYGOTES OF A FAMILY WITH ENDOTHELIAL DYSFUNCTION AND INCREASED ARTERIAL WALL THICKNESS in ATHEROSCLEROSIS SUPPLEMENTS, vol 11, issue 2, pp 67-672010In: ATHEROSCLEROSIS SUPPLEMENTS, Elsevier Science B.V., Amsterdam. , 2010, Vol. 11, no 2, p. 67-67Conference paper (Refereed)
    Abstract [en]

    n/a

  • 28.
    Laskar, Amit
    et al.
    Linköping University, Department of Medical and Health Sciences, Pharmacology. Linköping University, Faculty of Health Sciences.
    Eilertsen, Jonas
    Linköping University, Department of Clinical and Experimental Medicine, Experimental Pathology. Linköping University, Faculty of Health Sciences.
    Li, Wei
    Linköping University, Department of Medical and Health Sciences, Pharmacology. Linköping University, Faculty of Health Sciences.
    Yuan, Xi-Ming
    Linköping University, Department of Clinical and Experimental Medicine, Experimental Pathology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Occupational and Environmental Medicine Center.
    SPION primes THP1 derived M2 macrophages towards M1-like macrophages2013In: Biochemical and Biophysical Research Communications - BBRC, ISSN 0006-291X, E-ISSN 1090-2104, Vol. 441, no 4, p. 737-742Article in journal (Refereed)
    Abstract [en]

    Potentially, cellular iron regulates functional plasticity in macrophages yet; interaction of functionally polarized macrophages with iron-oxide nanoparticles has never been studied. We found that monocyte differentiation alters cellular ferritin and cathepsin L levels and induces functional polarization in macrophages. Iron in super paramagnetic iron-oxide nanoparticle (SPION) induces a phenotypic shift in THP1 derived M2 macrophages towards a high CD86+ macrophage subtype. This phenotypic shift was accompanied by up-regulated intracellular levels of ferritin and cathepsin L in M2 macrophages, which we found as a characteristic hallmark of M1 macrophages. Atherogenic oxysterols reduce phagocytic activity in both macrophage subtypes and thus these cells may escape detection by ironoxide nanoparticles (INPs) in-vivo.

  • 29.
    Laskar, Amit
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Experimental Pathology. Linköping University, Faculty of Health Sciences.
    Ghosh, Moumita
    Linköping University, Department of Clinical and Experimental Medicine, Experimental Pathology. Linköping University, Faculty of Health Sciences.
    Iqbal Khattak, Sikander
    Linköping University, Department of Clinical and Experimental Medicine, Experimental Pathology. Linköping University, Faculty of Health Sciences.
    Li, Wei
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
    Yuan, Xi-Ming
    Linköping University, Department of Clinical and Experimental Medicine, Experimental Pathology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Occupational and Environmental Medicine Center.
    Degradation of superparamagnetic iron oxide nanoparticle-induced ferritin by lysosomal cathepsins and related immune response2012In: Nanomedicine, ISSN 1743-5889, E-ISSN 1748-6963, Vol. 7, no 5, p. 705-717Article in journal (Refereed)
    Abstract [en]

    Aim: To examine the physiological impact of superparamagnetic iron oxide nanoparticles (SPIONs) on cell function and its interaction with oxysterol laden cells. Materials andamp; methods: Intracellular iron was determined by Prussian blue staining. Cellular ferritin, cathepsin L and ferroportin were analyzed by flow cytometry and fluorescence microscopy. Cytokine secretion was determined by ELISA and immunoblotting. Results: In U937 and THP 1 cells, we did not detect any loss of cell viability on SPION loading. Desferrioxamine prevents induction of both ferritin and cathepsin L by SPIONs. Inhibition of lysosomal cathepsins upregulates both endogenous- and SPION-induced ferritin. SPION loading induces membranous ferroportin and incites secretion of ferritin, TNF-alpha and IL-10. 7 beta-hydroxycholesterol exposure reduces SPION uptake by cells. Conclusion: SPION loading results in upregulation of lysosomal cathepsin, membranous ferroportin and ferritin degradation, which is associated with secretion of both pro- and anti-inflammatory cytokines. A reduced SPION uptake by oxysterol-laden cells may lead to a compromised MRI with elevated cathepsins and ferritin.

  • 30.
    Levels, Johannes HM
    et al.
    Department of Experimental Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.
    Geurts, Pierre
    Department of Electrical Engineering and Computer Science & GIGA-research, University of Liège, Belgium.
    Karlsson, Helen
    Linköping University, Department of Clinical and Experimental Medicine, Occupational and Environmental Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Occupational and Environmental Medicine Centre.
    Marée, Raphaël
    GIGA Bioinformatics Platform, University of Liège, Belgium.
    Ljunggren, Stefan
    Linköping University, Department of Clinical and Experimental Medicine, Occupational and Environmental Medicine. Linköping University, Faculty of Health Sciences.
    Fornander, Louise
    Linköping University, Department of Clinical and Experimental Medicine, Occupational and Environmental Medicine. Linköping University, Faculty of Health Sciences.
    Wehenkel, Louis
    Department of Electrical Engineering and Computer Science & GIGA-research, University of Liège, Belgium.
    Lindahl, Mats
    Linköping University, Department of Clinical and Experimental Medicine, Occupational and Environmental Medicine. Linköping University, Faculty of Health Sciences.
    Stroes, Erik SG
    Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.
    Kuivenhoven, Jan A
    Department of Experimental Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.
    Meijers, Joost CM
    Department of Experimental Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.
    High-density Lipoprotein proteome dynamics in human endotoxemia2011In: Proteome Science, ISSN 1477-5956, E-ISSN 1477-5956, Vol. 9, no 34Article in journal (Refereed)
    Abstract [en]

    Background: A large variety of proteins involved in inflammation, coagulation, lipid-oxidation and lipid metabolism have been associated with high-density lipoprotein (HDL) and it is anticipated that changes in the HDL proteome have implications for the multiple functions of HDL. Here, SELDI-TOF mass spectrometry (MS) was used to study the dynamic changes of HDL protein composition in a human experimental low-dose endotoxemia model. Ten healthy men with low HDL cholesterol (0.7+/-0.1 mmol/L) and 10 men with high HDL cholesterol levels (1.9+/-0.4mmol/L) were challenged with endotoxin (LPS) intravenously (1ng/kg bodyweight). We previously showed that subjects with low HDL cholesterol are more susceptible to an inflammatory challenge. The current study tested the hypothesis that this discrepancy may be related to differences in the HDL proteome.

    Results: Plasma drawn at 7 time-points over a 24 hour time period after LPS challenge was used for direct capture of HDL using antibodies against apolipoprotein A-I followed by subsequent SELDI-TOF MS profiling. Upon LPS administration, profound changes in 21 markers (adjusted p-value<0.05) were observed in the proteome in both study groups. These changes were observed 1 hour after LPS infusion and sustained up to 24 hours, but unexpectedly were not different between the 2 study groups. Hierarchical clustering of the protein spectra at all time points of all individuals revealed 3 distinct clusters, which were largely independent of baseline HDL cholesterol levels but correlated with paraoxonase 1 activity. The acute phase protein serum amyloid A-1/2 (SAA-1/2) was clearly upregulated after LPS infusion in both groups and comprised both native and N-terminal truncated variants that were identified by two-dimensional gel electrophoresis and mass spectrometry. Individuals of one of the clusters were distinguished by a lower SAA-1/2 response after LPS challenge and a delayed time-response of the truncated variants.

    Conclusions: This study shows that the semi-quantitative differences in the HDL proteome as assessed by SELDI-TOF MS cannot explain why subjects with low HDL cholesterol are more susceptible to a challenge with LPS than those with high HDL cholesterol. Instead the results indicate that hierarchical clustering could be useful to predict HDL functionality in acute phase responses towards LPS.

  • 31.
    Li, Wei
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
    Laskar, Amit
    Linköping University, Department of Clinical and Experimental Medicine, Experimental Pathology. Linköping University, Faculty of Health Sciences.
    Sultana, Nargis
    Linköping University, Department of Clinical and Experimental Medicine, Experimental Pathology. Linköping University, Faculty of Health Sciences.
    Osman, Ehab
    Linköping University, Department of Clinical and Experimental Medicine, Experimental Pathology. Linköping University, Faculty of Health Sciences.
    Ghosh, Moumita
    Linköping University, Department of Clinical and Experimental Medicine, Experimental Pathology. Linköping University, Faculty of Health Sciences.
    Li, Qianqian
    Linköping University, Department of Clinical and Experimental Medicine, Experimental Pathology. Linköping University, Faculty of Health Sciences.
    Yuan, Ximing
    Linköping University, Department of Clinical and Experimental Medicine, Experimental Pathology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Occupational and Environmental Medicine Center.
    Cell death induced by 7-oxysterols via lysosomal and mitochondrial pathways is p53-dependent2012In: Free Radical Biology & Medicine, ISSN 0891-5849, E-ISSN 1873-4596, Vol. 53, no 11, p. 2054-2061Article in journal (Refereed)
    Abstract [en]

    Oxysterol accumulation and p53 expression mainly in macrophages have been associated with cell death and necrotic core formation in human atheroma progression. Oxidative stress and lysosomal membrane permeabilization (LMP) in macrophages are important causes of macrophage apoptosis. However, it is not understood how p53 and oxysterols interact in the process. We show here that 7-oxysterols induce endogenous full-length p53 and phospho-p53 (p53-Ser15) in both nucleus and cytoplasm of THP1 and J774 cells, which is followed by cellular oxidative stress and apoptotic cell death. The role of p53 in 7-oxysterol-mediated cell death is further investigated in temperature sensitive p53-transfected (M1-t-p53) and in p53-deficient (M1) cells. These results reveal that 7-oxysterols induce induction and nuclear translocation of p53 in M1-t-p53 cells, which in turn enhances LMP, mitochondrial translocation of Bax, mitochondrial membrane permeabilization, cytosolic release of cytochrome c, and cell death. Most importantly, the above effects of 7-oxysterols were not observed in p53-deficient M1 cells. The findings reveal that 7-oxysterol-induced cell death occurs via p53-dependent pathways. Subsequent p53 nuclear translocation and induction of wild-type and phosphorylated p53 are early steps in oxysterol-induced lysosomal-mitochondrial pathways involved in cell death.

  • 32.
    Lindh, Jonas
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Neurology. Linköping University, Faculty of Health Sciences.
    Söderkvist, Peter
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
    Fredrikson, Mats
    Linköping University, Department of Clinical and Experimental Medicine, Occupational and Environmental Medicine. Linköping University, Faculty of Health Sciences.
    Hosseininia, Shahzad
    Yrkes och miljömedicin, Medicinska fakulteten, Teherans universitet, Teheran, Iran.
    Tondel, Martin
    Arbets- och miljömedicin, Sahlgrenska Universitetssjukhuset, Göteborg.
    Persson, Bodil
    Linköping University, Department of Clinical and Experimental Medicine, Occupational and Environmental Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Occupational and Environmental Medicine Center.
    Vrethem, Magnus
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Neurophysiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Neurology.
    Polymorphisms of GSTT1, GSTM1 and EPHX genotypes in patients with cryptogenic polyneuropathy: a case control study2011In: Brain and Behavior, ISSN 2162-3279, E-ISSN 2162-3279, Vol. 1, no 2, p. 135-141Article in journal (Refereed)
    Abstract [en]

    The aim of this study was to analyze whether polymorphisms for the null alleles of Glutathione S-Transferase Mu-1 (GSTM1) and Theta-1 (GSTT1) and a low activity genetic variation of epoxide hydrolase exon three (EPHX*3) affect the risk of developing polyneuropathy. The enzymes of these genes are important in the metabolism of toxic compounds. 79 patients with cryptogenic polyneuropathy (equivalent to chronic idiopathic axonal neuropathy) and 398 controls were tested for the genetic polymorphism. Medical records were reviewed to collect data regarding clinical findings at diagnosis, and exposure data was collected via questionnaires. The odds ratios (OR) for the null forms of GSTM1 and GSTT1 and the normal activity YY form of EPHX*3 were close to one except GSTT1, which reached 1.86. The highest risk of polyneuropathy was found in smokers with GSTT1 null, who had a 3.7 times increased risk. Interactions between genes were analyzed and confirmed the increased odds ratio for GSTT1, which was strongest if the patients had the low activity HH form of EPHX*3 (OR 2.37). Our hypothesis is that the GSTT1 null polymorphism may be related to an impaired metabolism of toxic substances that could lead to nerve damage in the peripheral nervous system.

  • 33.
    Ljunggren, Stefan A
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences.
    Helmfrid, Ingela
    Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Occupational and Environmental Medicine Center.
    Salihovic, Samira
    Örebro University, Sweden.
    van Bavel, Bert
    Örebro University, Sweden.
    Wingren, Gun
    Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences.
    Lindahl, Mats
    Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences.
    Karlsson, Helen
    Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Occupational and Environmental Medicine Center.
    Persistent organic pollutants distribution in lipoprotein fractions in relation to cardiovascular disease and cancer.2014In: Environment International, ISSN 0160-4120, E-ISSN 1873-6750, Vol. 65, p. 93-9Article in journal (Refereed)
    Abstract [en]

    Persistent organic pollutants (POPs) are lipophilic environmental toxins that have been associated with cardiovascular disease (CVD) and cancer. The aim of this study was to investigate the concentrations of POPs in human high and low/very low-density lipoproteins (HDL and LDL/VLDL) and the possible association with CVD and cancer occurrence in individuals living in a contaminated area. Lipoproteins from 28 individuals (7 healthy controls, 8 subjects with cancer, 13 subjects with CVD) were isolated and the fraction-specific concentration of 20 different POPs was analyzed by high resolution gas chromatography/high resolution mass spectrometry. The activity of Paraoxonase 1 (PON1), an anti-oxidant in HDL, was determined in plasma of these 28 subjects and additional 50 subjects from the same area excluding diseases other than cancer or CVD. Fourteen polychlorinated biphenyls (PCBs) and three organochlorine pesticides were detected, and especially highly chlorinated PCBs were enriched in lipoproteins. Significantly higher concentrations of POPs were found among individuals with CVD or cancer compared to controls. Principal component analyses showed that POP concentrations in HDL were more associated with CVD, while POP concentrations in LDL/VLDL were more associated with cancer. PON1 activity was negatively correlated to sumPCB and a co-variation between decreased arylesterase-activity, increased PCB concentrations and CVD was found. This study shows that POPs are present in lipoproteins and were more abundant in individuals with CVD or cancer compared to healthy controls. The results also indicate that PCB exposure is accompanied by reduced PON1 activity that could impair the HDL function to protect against oxidation.

  • 34.
    Ljunggren, Stefan
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Occupational and Environmental Medicine. Linköping University, Faculty of Health Sciences.
    Karlsson, Helen
    Linköping University, Department of Clinical and Experimental Medicine, Occupational and Environmental Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Occupational and Environmental Medicine Center.
    Mörtstedt, Harriet
    Occupational and Environmental Medicine, Lund University Hospital, Lund.
    Hellström, L.
    Internal Medicine and Environmental Medicine and Public Health, Oskarshamn Hospital, Oskarshamn, Sweden.
    Perk, J.
    Internal Medicine and Environmental Medicine and Public Health, Oskarshamn Hospital, Oskarshamn, Sweden.
    Besler, C.
    Cardiovascular Center, Zurich University Hospital, Switzerland.
    Landmesser, U.
    Cardiovascular Center, Zurich University Hospital, Switzerland.
    von Eckardstein, A.
    Institute for Clinical Chemistry, Zurich University Hospital, Zurich, Switzerland.
    Lindahl, Mats
    Linköping University, Department of Clinical and Experimental Medicine, Occupational and Environmental Medicine. Linköping University, Faculty of Health Sciences.
    Changes in Human Liportein Composition in Patients with Acute Coronary Syndrome2011In: Atherosclerosis Supplements, ISSN 1567-5688, E-ISSN 1878-5050, Vol. 12, no 1, p. 14-14Article in journal (Other academic)
    Abstract [en]

    The protein composition of lipoproteins may serve as biomarkers or reveal underlying mechanisms during different states of disease. Here we have analysed the protein composition of LDL and HDL from patients with acute coronary syndrome (ACS) and patients receiving statins after previous ACS. Plasma samples were obtained from males, namely 12 healthy donors, 9 patients with ACS and 7 stable patients receiving statin treatment after previous ACS. LDL and HDL were isolated by two-step density ultracentrifugation. LDL proteins were analysed with two-dimensional gel electrophoresis and mass spectrometry. Paraoxonase 1 (PON-1) in HDL was analyzed with  SDSPAGE/Western Blot.

    Concentrations of apo A-IV, a1-antitrypsin and transthyretin were significantly increased (P < 0.05) in LDL from patients with ACS compared to healthy controls. In patients receiving statins, a1-antitrypsin remained increased while serum amyloid A4 was decreased. By western blot analysis, a non-significant increase in PON-1 was found in HDL from patients with ACS. Interestingly, a truncated form of PON-1 was detected in all patients with ACS but not in any of the controls.

    In conclusion, we confirm previous findings that LDL-associated transthyretin is a possible biomarker of myocardial infarction. Moreover, the increased concentration of the inflammatory marker a1-antitrypsin in LDL from both ACS patients and stable patients after ACS indicate that the enrichment does not only reflect an acute phase response. The presence of a truncated form of the antioxidant protein PON-1 in HDL may explain previous findings showing increased amounts but lower activity of PON-1 in patients with ACS.

  • 35.
    Ljunggren, Stefan
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences.
    Levels, Johannes H M
    Department of Vascular Medicine, Academic Medical Centre, Amsterdam, The Netherlands.
    Turkina, Maria V
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Health Sciences.
    Sundberg, Sofie
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Health Sciences.
    Bochem, Andrea E
    Department of Vascular Medicine, Academic Medical Centre, Amsterdam, The Netherlands.
    Hovingh, Kees
    Department of Vascular Medicine, Academic Medical Centre, Amsterdam, The Netherlands.
    Holleboom, Adriaan G
    Department of Vascular Medicine, Academic Medical Centre, Amsterdam, The Netherlands.
    Lindahl, Mats
    Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences.
    Kuivenhoven, Jan Albert
    University of Groningen, Groningen, The Netherlands.
    Karlsson, Helen
    Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Occupational and Environmental Medicine Center.
    ApoA-I mutations, L202P and K131del, in HDL from heterozygotes with low HDL-C2014In: PROTEOMICS - Clinical Applications, ISSN 1862-8346, E-ISSN 1862-8354, Vol. 8, no 3-4, p. 241-250Article in journal (Refereed)
    Abstract [en]

    PURPOSE: Mutations in apolipoprotein A-I (apoA-I) may affect plasma high-density lipoprotein (HDL) cholesterol levels and the risk for cardiovascular disease but little is known about the presence and effects of circulating apoA-I variants. This study investigates whether the apoA-I mutations, apoA-I(L202P) and apoA-I(K131del) , are present on plasma HDL particles derived from heterozygote carriers and whether this is associated to changes in HDL protein composition.

    EXPERIMENTAL DESIGN: Plasma HDL of heterozygotes for either apoA-I(L202P) or apoA-I(K131del) and family controls was isolated using ultracentrifugation. HDL proteins were separated by 2DE and analyzed by MS.

    RESULTS: ApoA-I peptides containing apoA-I(L202P) or apoA-I(K131del) were identified in HDL from heterozygotes. The apoA-I(L202P) mutant peptide was less abundant than wild-type peptide while the apoA-I(K131del) mutant peptide was more abundant than wild-type peptide in the heterozygotes. Two-dimensional gel electrophoresis analyses indicated that, compared to controls, HDL in apoA-I(L202P) carriers contained less apoE and more zinc-α-2-glycoprotein while HDL from the apoA-I(K131del) heterozygotes contained more alpha-1-antitrypsin and transthyretin.

    CONCLUSIONS AND CLINICAL RELEVANCE: Both apoA-I(L202P) and apoA-I(K131del) were identified in HDL. In heterozygotes, these mutations have markedly differential effects on the concentration of wild-type apoA-I in the circulation, as well as the HDL proteome, both of which might affect the clinical phenotype encountered in the heterozygous carriers.

  • 36.
    Louca, Sofia
    et al.
    Karolinska Institute, Sweden; SCON, Sweden.
    Christidis, Nikolaos
    Karolinska Institute, Sweden; SCON, Sweden.
    Ghafouri, Bijar
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center. Östergötlands Läns Landsting, Heart and Medicine Center, Occupational and Environmental Medicine Center.
    Gerdle, Björn
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
    Svensson, Peter
    Karolinska Institute, Sweden; SCON, Sweden; University of Aarhus, Denmark.
    List, Thomas
    SCON, Sweden; Malmö University, Sweden.
    Ernberg, Malin
    Karolinska Institute, Sweden; SCON, Sweden.
    Serotonin, glutamate and glycerol are released after the injection of hypertonic saline into human masseter muscles - a microdialysis study2014In: Journal of Headache and Pain, ISSN 1129-2369, E-ISSN 1129-2377, Vol. 15Article in journal (Refereed)
    Abstract [en]

    Chronic myalgia is associated with higher muscle levels of certain algesic biomarkers. The aim of this study was to investigate if hypertonic saline-induced jaw myalgia also leads to release of such biomarkers and if there were any sex differences in this respect. Healthy participants, 15 men and 15 aged-matched women (25.7 +/- 4.3 years) participated. Intramuscular microdialysis into masseter muscles was performed to sample serotonin (5-HT), glutamate, lactate, pyruvate, glucose and glycerol. After 2 hours 0.2 mL hypertonic saline (58.5 mg/mL) was injected into the masseter on one side and 0.2 mL isotonic saline (9 mg/mL) into the contralateral masseter close to the microdialysis catheter. Microdialysis continued for 1 hour after the injections. Pressure pain thresholds (PPT) and pain were assessed before and after injections. The median (IQR) peak pain intensity (0-100 visual analogue scale) after hypertonic saline was 52.5 (38.0) and after isotonic saline 7.5 (24.0) (p less than 0.05). 5-HT, glutamate and glycerol increased after hypertonic saline injection (p less than 0.05). Lactate, pyruvate and glucose showed no change. PPT after microdialysis was reduced on both sides (p less than 0.05) but without side differences. Pain after hypertonic saline injection correlated positively to 5-HT (p less than 0.05) and negatively to glycerol (p less than 0.05). 5-HT, glutamate and glycerol increased after a painful hypertonic saline injection into the masseter muscle, but without sex differences. Since increased levels of 5-HT and glutamate have been reported in chronic myalgia, this strengthens the validity of the pain model. Glycerol warrants further investigations.

  • 37.
    Miah, Sayem
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Experimental Pathology. Linköping University, Faculty of Health Sciences.
    Zadeh, Shahram Nour Mohammad
    Linköping University, Department of Clinical and Experimental Medicine, Experimental Pathology. Linköping University, Faculty of Health Sciences.
    Yuan, Xi-Ming
    Linköping University, Department of Clinical and Experimental Medicine, Experimental Pathology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Occupational and Environmental Medicine Center.
    Li, Wei
    Linköping University, Department of Clinical and Experimental Medicine, Experimental Pathology. Linköping University, Faculty of Health Sciences.
    Expression of Egr1 and p53 in human carotid plaques and apoptosis induced by 7-oxysterol or p53.2013In: Experimental and Toxicological Pathology, ISSN 0940-2993, E-ISSN 1618-1433, Vol. 65, no 5, p. 677-682Article in journal (Refereed)
    Abstract [en]

    Egr-1 and p53 are involved in pathology of both atherosclerosis and cancer. However, it is unknown whether p53 and Egr1 are interactively involved in apoptosis in atherosclerosis. We found that in human carotid plaques, the expression of p53 was inversely correlated with Egr1. In U937 cells, 7 beta-hydroxycholesterol and 7-ketocholesterol induced production of reactive oxygen species (ROS), transient up-regulation of Egr1 followed by late induction of p53 and apoptosis. Cells with nuclear fragmentation induced by 7-oxysterol or p53 showed increased levels of p53, but decreased levels of Egr1. In conclusion, ROS induced by 7-oxysterols may function as an early initiator of Egr1 expression. The late induced p53 by 7-oxysterols contributes to apoptotic cell death and is linked to the reduction of Egr1 levels, which resembles the differential expression of p53 and Egr1 in human atheroma progression.

  • 38.
    Olausson, Patrik
    et al.
    Linköping University, Department of Medical and Health Sciences, Rehabilitation Medicine. Linköping University, Faculty of Health Sciences.
    Gerdle, Björn
    Linköping University, Department of Medical and Health Sciences, Rehabilitation Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
    Ghafouri, Nazdar
    Linköping University, Department of Medical and Health Sciences, Rehabilitation Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
    Karlsson, Linn
    Linköping University, Department of Medical and Health Sciences, Rehabilitation Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
    Larsson, Britt
    Linköping University, Department of Medical and Health Sciences, Rehabilitation Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
    Ghafouri, Bijar
    Linköping University, Department of Medical and Health Sciences, Rehabilitation Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center. Östergötlands Läns Landsting, Heart and Medicine Center, Occupational and Environmental Medicine Center.
    Relative recovery over time – an in vivo microdialysisstudy of human skeletal muscle2013In: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686, Vol. 73, no 1, p. 10-16Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    The microdialysis technique is a method for sampling endogenous molecules from the interstitial compartments of varying tissues and relies on diffusion of molecules between the tissue and a perfusate via a membrane. Such samples do not allow determination of the true interstitial concentration but only a certain percentage. This gives rise to one of the most crucial parameter that needs to be considered for a dependable microdialysis; the relative recovery. Relative recovery states the efficiency of which an analyte is extracted from its external medium. Aim. To investigate the relative recovery of small molecules (< 20 kDa) such as lactate, fluid recovery and the reproducibility of the relative recovery at group and individual level of the microdialysis technique applied in muscle.

    MATERIALS AND METHODS:

    Using in vivo microdialysis of the trapezius muscle of 65 women from two separate occasions 4-6 months apart. Relative recovery of small molecules was measured from samples collected every 20 min during a period of 220 min.

    RESULTS:

    Good reproducibility at group level of catheters with cut-offs 100 and 20kDa were found. Furthermore, there was a high and steady relative recovery with an overall good fluid recovery. Poor reproducibility was found at the individual level for both catheters.

    CONCLUSIONS:

    This study demonstrates that when using microdialysis in skeletal muscle relative recovery is stable over time and is not affected by low-force exercise. Although there is a good reproducibility at group level this is not the case at the individual level. Thus in vivo, the relative recovery should be determined for each test subject and at each test occasion.

  • 39.
    Olausson, Patrik
    et al.
    Linköping University, Department of Medical and Health Sciences, Rehabilitation Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
    Gerdle, Björn
    Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center. Linköping University, Department of Medical and Health Sciences, Division of Community Medicine.
    Ghafouri, Nazdar
    Linköping University, Department of Medical and Health Sciences, Rehabilitation Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
    Larsson, Britt
    Linköping University, Department of Medical and Health Sciences, Rehabilitation Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
    Ghafouri, Bijar
    Linköping University, Department of Medical and Health Sciences, Rehabilitation Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center. Östergötlands Läns Landsting, Heart and Medicine Center, Occupational and Environmental Medicine Center.
    Identification of Proteins from Interstitium of Trapezius Muscle in Women with Chronic Myalgia Using Microdialysis in Combination with Proteomics2012In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 7, no 12Article in journal (Refereed)
    Abstract [en]

    Background: Microdialysis (MD) of the trapezius muscle has been an attractive technique to investigating small molecules and metabolites in chronic musculoskeletal pain in human. Large biomolecules such as proteins also cross the dialysis membrane of the catheters. In this study we have applied in vivo MD in combination with two dimensional gel electrophoresis (2-DE) and mass spectrometry to identify proteins in the extracellular fluid of the trapezius muscle. Materials and Methods: Dialysate from women with chronic trapezius myalgia (TM; n = 37), women with chronic wide spread pain (CWP; n = 18) and healthy controls (CON; n = 22) was collected from the trapezius muscle using a catheter with a cut-off point of 100 kDa. Proteins were separated by two-dimensional gel electrophoresis and visualized by silver staining. Detected proteins were identified by nano liquid chromatography in combination with tandem mass spectrometry. Results: Ninety-seven protein spots were identified from the interstitial fluid of the trapezius muscle; 48 proteins in TM and 30 proteins in CWP had concentrations at least two-fold higher or lower than in CON. The identified proteins pertain to several functional classes, e.g., proteins involved in inflammatory responses. Several of the identified proteins are known to be involved in processes of pain such as: creatine kinase, nerve growth factor, carbonic anhydrase, myoglobin, fatty acid binding protein and actin aortic smooth muscle. Conclusions: In this study, by using in vivo microdialysis in combination with proteomics a large number of proteins in muscle interstitium have been identified. Several of the identified proteins were at least two-fold higher or lower in chronic pain patients. The applied techniques open up for the possibility of investigating protein changes associated with nociceptive processes of chronic myalgia. © 2012 Olausson et al.

  • 40.
    Palstam, Annie
    et al.
    Gothenburg University, Sweden; University of Gothenburg Centre Person Centre Care GPCC, Sweden.
    Larsson, Anette
    Gothenburg University, Sweden; University of Gothenburg Centre Person Centre Care GPCC, Sweden.
    Bjersing, Jan
    Gothenburg University, Sweden.
    Lofgren, Monika
    Karolinska Institute, Sweden.
    Ernberg, Malin
    Karolinska Institute, Sweden.
    Bileviciute-Ljungar, Lndre
    Karolinska Institute, Sweden.
    Ghafouri, Bijar
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center. Östergötlands Läns Landsting, Heart and Medicine Center, Occupational and Environmental Medicine Center.
    Sjörs, Anna
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Health Sciences.
    Larsson, Britt
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
    Gerdle, Björn
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
    Kosek, Eva
    Karolinska Institute, Sweden; Karolinska Institute, Sweden.
    Mannerkorpi, Kaisa
    Gothenburg University, Sweden; University of Gothenburg Centre Person Centre Care GPCC, Sweden .
    PERCEIVED EXERTION AT WORK IN WOMEN WITH FIBROMYALGIA: EXPLANATORY FACTORS AND COMPARISON WITH HEALTHY WOMEN2014In: Journal of Rehabilitation Medicine, ISSN 1650-1977, E-ISSN 1651-2081, Vol. 46, no 8, p. 773-780Article in journal (Refereed)
    Abstract [en]

    Objective: To investigate perceived exertion at work in women with fibromyalgia. Design: A controlled cross-sectional multi-centre study. Subjects and methods: Seventy-three women with fibromyalgia and 73 healthy women matched by occupation and physical workload were compared in terms of perceived exertion at work (0-14), muscle strength, 6-min walk test, symptoms rated by Fibromyalgia Impact Questionnaire (FIQ), work status (25-100%), fear avoidance work beliefs (0-42), physical activity at work (7-21) and physical workload (1-5). Spearmans correlation coefficient and linear regression analysis were conducted. Results: Perceived exertion at work was significantly higher in the fibromyalgia group than in the reference group (p=0.002), while physical activity at work did not differ between the groups. Physical capacity was lower and symptom severity higher in fibromyalgia compared with references (pless than0.05). In fibromyalgia, perceived exertion at work showed moderate correlation with physical activity at work, physical workload and fear avoidance work beliefs (r(s) = 0.53 0.65, pless than0.001) and a fair correlation with anxiety (r(s) = 0.26, p=0.027). Regression analysis indicated that the physical activity at work and fear avoidance work beliefs explained 50% of the perceived exertion at work. Conclusion: Women with fibromyalgia perceive an elevated exertion at work, which is associated with physical work-related factors and factors related to fear and anxiety.

  • 41.
    Persson, Bodil
    et al.
    Skåne University Hospital, Sweden.
    Vrethem, Magnus
    Linköping University, Department of Clinical and Experimental Medicine, Neurology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Neurology.
    Murgia, Nicola
    University of Perugia, Italy.
    Lindh, Jonas
    Ryhov County Hospital, Sweden.
    Hällsten, Anna-Lena
    Linköping University, Department of Clinical and Experimental Medicine, Occupational and Environmental Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Occupational and Environmental Medicine Center.
    Fredrikson, Mats
    Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences.
    Tondel, Martin
    Uppsala University, Sweden.
    Urinary 2,5-hexanedione excretion in cryptogenic polyneuropathy compared to the general Swedish population2013In: Journal of Occupational Medicine and Toxicology, ISSN 1745-6673, E-ISSN 1745-6673, Vol. 8Article in journal (Refereed)
    Abstract [en]

    Background

    2,5-hexanedione (2,5-HD) is the main neurotoxic metabolite of methyl-n-butyl ketone (MBK) and n-hexane, and known to cause polyneuropathy. The aim of our study was to compare the urinary levels of 2,5-HD between cases with cryptogenic polyneuropathy and the general Swedish population, and to elucidate the role of certain external factors.

    Methods

    Morning urine samples were collected from 114 cases with cryptogenic polyneuropathy (77 men and 37 women) and 227 referents (110 men and 117 women) randomly selected from the population registry. None had any current occupational exposure to n-hexane or MBK. The urine samples were analysed by a gas chromatographic method based on acidic hydrolysis.

    Results

    Cases had statistically higher urinary levels of 2,5-HD (0.48 mg/L) than the general population (0.41 mg/L) and men higher excretion than women (0.48 mg/L and 0.38 mg/L, respectively). There was no difference in 2,5-HD levels between current smokers and non-smokers. Occupational exposure to xylene, alcohol consumption and ever exposed to general anaesthesia were associated with lower excretion in men while for occupational exposure to nitrous oxide in women higher excretion was seen. Higher excretion of 2,5 HD was inversely related to increasing age.

    Conclusions

    Significantly higher levels of urinary 2,5-HD were seen in men and cryptogenic polyneuropathy cases seemingly unexposed to n-hexane. Hypothetically, this might be due to either differences in metabolic patterns or some concealed exposure. The difference in means between cases and the general population is small and can therefore not allow any firm conclusions of the causality, however.

  • 42.
    Pettersson, C
    et al.
    Wallenberg Laboratory for Cardiovasc Research, Gothenburg.
    Karlsson, H
    Linköping University, Department of Clinical and Experimental Medicine, Occupational and Environmental Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Occupational and Environmental Medicine Centre. Östergötlands Läns Landsting.
    Fagerberg, B
    Wallenberg Laboratory for Cardiovasc Research, Gothenburg.
    Stahlman, M
    Wallenberg Laboratory for Cardiovasc Research, Gothenburg.
    Larsson, T
    Wallenberg Laboratory for Cardiovasc Research, Gothenburg.
    Lindahl, Mats
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Boren, J
    Wallenberg Laboratory for Cardiovasc Research, Gothenburg.
    Wiklund, O
    Wallenberg Laboratory for Cardiovasc Research, Gothenburg.
    Fogelstrand, L
    Wallenberg Laboratory for Cardiovasc Research, Gothenburg.
    LDL-ASSOCIATED LYSOZYME AND apoJ-SPECIFIC DISTRIBUTION IN INDIVIDUALS WITH TYPE 2 DIABETES AND THE METABOLIC SYNDROME in ATHEROSCLEROSIS SUPPLEMENTS, vol 11, issue 2, pp 114-1142010In: ATHEROSCLEROSIS SUPPLEMENTS, Elsevier Science B.V., Amsterdam. , 2010, Vol. 11, no 2, p. 114-114Conference paper (Refereed)
    Abstract [en]

    n/a

  • 43.
    Pettersson, Camilla
    et al.
    The Wallenberg Laboratory, Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
    Karlsson, Helen
    Linköping University, Department of Clinical and Experimental Medicine, Occupational and Environmental Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Occupational and Environmental Medicine Centre.
    Ståhlman, Marcus
    The Wallenberg Laboratory, Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
    Larsson, Thomas
    The Wallenberg Laboratory, Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
    Fagerberg, Björn
    The Wallenberg Laboratory, Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
    Lindahl, Mats
    Linköping University, Department of Clinical and Experimental Medicine, Occupational and Environmental Medicine. Linköping University, Faculty of Health Sciences.
    Wiklund, Olov
    The Wallenberg Laboratory, Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
    Borén, Jan
    The Wallenberg Laboratory, Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
    Fogelstrand, Linda
    The Wallenberg Laboratory, Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
    LDL-associated apolipoprotein J and lysozyme are associated with atherogenic properties of LDL found in type 2 diabetes and the metabolic syndrome2011In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 269, no 3, p. 306-321Article in journal (Refereed)
    Abstract [en]

    Objectives  Exchangeable low-density lipoprotein (LDL)-associated proteins can affect the atherogenic properties of LDL. Our aim was to analyze the protein composition of LDL from individuals with or without type 2 diabetes and the metabolic syndrome (T2DM) in relation to other LDL-particle characteristics, to assess whether certain proteins associate more with certain subclasses of LDL typical for T2DM, such as small, apoCIII-rich LDL. Design  LDL from two cohorts of 61-year-old men (n = 19 and 64) with or without T2DM was isolated using size-exclusion chromatography or deuterium oxide-based ultracentrifugation. LDL-associated proteins were identified using mass spectrometry and quantified using two-dimensional gel electrophoresis or enzyme-linked immunosorbent assay. Differently expressed LDL-associated proteins apolipoprotein (apo)J and lysozyme were also measured in serum from a third cohort of women (n = 71) with or without T2DM. Lysozyme binding to advanced glycation end product (AGE)-LDL was examined in vitro. Results  ApoJ and lysozyme were increased in LDL particles with increased apoCIII content and decreased cholesterol content. When isolated with SEC, LDL from individuals with T2DM contained more apoJ and lysozyme and less apoA1 than LDL from control individuals. LDL content of apoJ correlated with a smaller LDL-particle size. Serum levels of lysozyme, but not apoJ, were increased in individuals with T2DM. In vitro, lysozyme associated more with AGE-LDL than with unmodified LDL. Conclusions  Our results indicate that apoJ and lysozyme are increased in LDL with characteristics of small dense LDL in T2DM. Small dense LDL is easily glycated, and the increased affinity of lysozyme for AGE-LDL provides a possible partial explanation for an increase of lysozyme from those with type 2 diabetes.

  • 44.
    Ronn, M
    et al.
    Uppsala University.
    Ortiz-Nieto, F
    Uppsala University.
    Karlsson, Helen
    Linköping University, Department of Clinical and Experimental Medicine, Occupational and Environmental Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Occupational and Environmental Medicine Centre.
    Kullberg, J
    Uppsala University.
    A rodent model for visceral obesity development evaluated by MRI in TOXICOLOGY LETTERS, vol 205, issue , pp S207-S2072011In: TOXICOLOGY LETTERS, Elsevier , 2011, Vol. 205, p. S207-S207Conference paper (Refereed)
    Abstract [en]

    n/a

  • 45.
    Rydén, Mireille
    et al.
    Linköping University, Department of Medical and Health Sciences, Cardiology. Linköping University, Faculty of Health Sciences.
    Garvin, Peter
    Linköping University, Department of Medical and Health Sciences, Division of Preventive and Social Medicine and Public Health Science. Linköping University, Faculty of Health Sciences.
    Kristenson, Margareta
    Linköping University, Department of Medical and Health Sciences, Division of Preventive and Social Medicine and Public Health Science. Linköping University, Faculty of Health Sciences.
    Leanderson, Per
    Linköping University, Department of Clinical and Experimental Medicine, Occupational and Environmental Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Occupational and Environmental Medicine Centre.
    Ernerudh, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    Jonasson, Lena
    Linköping University, Department of Medical and Health Sciences, Cardiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Cardiology UHL.
    Provitamin A carotenoids are independently associated with matrix metalloproteinase-9 in plasma samples from a general population2012In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 272, no 4, p. 371-384Article in journal (Refereed)
    Abstract [en]

    Background and aim:  Carotenoids in plasma are inversely associated with cardiovascular risk. Low levels can be explained by low dietary intake but also by a number of other factors including inflammatory activity. Given that matrix metalloproteinase (MMP)-9 has an important role in inflammation and cardiovascular disease, we hypothesized that circulating MMP-9 levels would be inversely related to total or single carotenoids in a general population cohort. Methods:  A well-characterized population-based cohort of 285 Swedish men and women (45-69 years) was used for the present study. The intake of carotenoid-rich fruits and vegetables was estimated from a food frequency questionnaire. Levels of MMP-9, C-reactive protein (CRP), interleukin (IL)-6 and six major carotenoids [β-cryptoxanthine, α-carotene, β-carotene, lutein (+ zeaxanthin) and lycopene] were determined in plasma. Results:  Lower plasma levels of total and single carotenoids were associated with lower dietary intake of carotenoids, older age, male sex, lower physical activity, higher alcohol consumption, higher body mass index (BMI), higher systolic and diastolic blood pressures, lower levels of total cholesterol and HDL cholesterol and higher levels of CRP, IL-6 and MMP-9. After multivariate adjustments, plasma levels of total carotenoids and provitamin A carotenoids (β-cryptoxanthine, α-carotene and β-carotene) remained independently associated with sex, dietary intake of carotenoids, BMI, HDL cholesterol and MMP-9, while associations with CRP and IL-6 were not maintained. Neither dietary intake of carotenoid-rich fruits and vegetables, nor vitamin supplement use was associated with MMP-9, CRP or IL-6 levels. Conclusion:  Plasma carotenoids were associated with a variety of factors including age, sex, dietary intake and metabolic variables. A new finding was the independent relationship in plasma between low provitamin A carotenoids and high MMP-9, suggesting a link between these carotenoids, matrix turnover and arterial remodelling. © 2012 The Association for the Publication of the Journal of Internal Medicine.

  • 46.
    Rönn, Monika
    et al.
    Uppsala University, Sweden.
    Kullberg, Joel
    Uppsala University, Sweden.
    Karlsson, Helen
    Linköping University, Department of Clinical and Experimental Medicine, Work and Environmental Science. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Occupational and Environmental Medicine Center.
    Berglund, Johan
    Uppsala University, Sweden.
    Malmberg, Filio
    Uppsala University, Sweden.
    Örberg, Jan
    Uppsala University, Sweden.
    Lind, Lars
    Uppsala University, Sweden.
    Ahlström, Håkan
    Uppsala University, Sweden.
    Lind, Monica P
    Uppsala University, Sweden.
    Bisphenol A exposure increases liver fat in juvenile fructose-fed Fischer 344 rats2013In: Toxicology, ISSN 0300-483X, E-ISSN 1879-3185, Vol. 303, p. 125-132Article in journal (Refereed)
    Abstract [en]

    Background

    Prenatal exposure to bisphenol A (BPA) has been shown to induce obesity in rodents. To evaluate if exposure also later in life could induce obesity or liver damage we investigated these hypothesises in an experimental rat model.

    Methods

    From five to fifteen weeks of age, female Fischer 344 rats were exposed to BPA via drinking water (0.025, 0.25 or 2.5 mg BPA/L) containing 5% fructose. Two control groups were given either water or 5% fructose solution. Individual weight of the rats was determined once a week. At termination magnetic resonance imaging was used to assess adipose tissue amount and distribution, and liver fat content. After sacrifice the left perirenal fat pad and the liver were dissected and weighed. Apolipoprotein A-I in plasma was analyzed by western blot.

    Results

    No significant effects on body weight or the weight of the dissected fad pad were seen in rats exposed to BPA, and MRI showed no differences in total or visceral adipose tissue volumes between the groups. However, MRI showed that liver fat content was significantly higher in BPA-exposed rats than in fructose controls (p = 0.04). BPA exposure also increased the apolipoprotein A-I levels in plasma (p < 0.0001).

    Conclusion

    We found no evidence that BPA exposure affects fat mass in juvenile fructose-fed rats. However, the finding that BPA in combination with fructose induced fat infiltration in the liver at dosages close to the current tolerable daily intake (TDI) might be of concern given the widespread use of this compound in our environment.

  • 47.
    Rönn, Monika
    et al.
    Uppsala University, Sweden.
    Lind, Monica
    Uppsala University, Sweden.
    Karlsson, Helen
    Linköping University, Department of Clinical and Experimental Medicine, Work and Environmental Science. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Occupational and Environmental Medicine Center.
    Cvek, Katarina
    The Swedish university of Agricultural Science, Uppsala, Sweden.
    Berglund, Johan
    Uppsala University, Sweden.
    Malmberg, Filip
    Uppsala University, Sweden.
    Örberg, Jan
    Uppsala University, Sweden.
    Lind, Lars
    Uppsala University, Sweden.
    Kullberg, Joel
    Uppsala University, Sweden.
    Quantification of total and visceral adipose tissue in fructose-fed rats using water-fat separated single Echo MRI2013In: Obesity, ISSN 1930-7381, E-ISSN 1930-739X, Vol. 21, no 9, p. E388-E395Article in journal (Refereed)
    Abstract [en]

    Objective: The aim of this study was to setup a rodent model for modest weight gain and an MRI-based quantification of body composition on a clinical 1.5 T MRI system for studies of obesity and environmental factors and their possible association. Design and Methods: Twenty-four 4-week-old female Fischer rats were divided into two groups: one exposed group (n=12) and one control group (n 12). The exposed group was given drinking water containing fructose (5% for 7 weeks, then 20% for 3 weeks). The control group was given tap water. Before sacrifice, whole body MRI was performed to determine volumes of total and visceral adipose tissue and lean tissue. MRI was performed using a clinical 1.5 T system and a chemical shift based technique for separation of water and fat signal from a rapid single echo acquisition. Fat signal fraction was used to separate adipose and lean tissue. Visceral adipose tissue volume was quantified using semiautomated segmentation. After sacrifice, a perirenal fat pad and the liver were dissected and weighed. Plasma proteins were analyzed by Western blot. Results: The weight gain was 5.2% greater in rats exposed to fructose than in controls (P=0.042). Total and visceral adipose tissue volumes were 5.2 cm(3) (P=0.017) and 3.1 cm(3) (P=0.019) greater, respectively, while lean tissue volumes did not differ. The level of triglycerides and apolipoprotein A-I was higher (P=0.034, P=0.005, respectively) in fructose-exposed rats. Conclusions: The setup induced and assessed a modest visceral obesity and hypertriglyceridemia, making it suitable for further studies of a possible association between environmental factors and obesity.

  • 48.
    Strom, Sofie
    et al.
    Karolinska Institute.
    Helmfrid, Ingela
    Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Occupational and Environmental Medicine Centre.
    Glynn, Anders
    Natl Food Adm Toxicol Lab, Uppsala, Sweden .
    Berglund, Marika
    Karolinska Institute.
    Nutritional and toxicological aspects of seafood consumption-An integrated exposure and risk assessment of methylmercury and polyunsaturated fatty acids2011In: ENVIRONMENTAL RESEARCH, ISSN 0013-9351, Vol. 111, no 2, p. 274-280Article in journal (Refereed)
    Abstract [en]

    Seafood consumption is associated with both risks and beneficial effects to human health. Consequently, an integrated exposure assessment of intake of toxic and nutritious agents in seafood is of importance prior to determination of dietary advisories. We have developed a probabilistic model for the estimation of simultaneous intake of methylmercury (MeHg) and long-chain n-3 polyunsaturated fatty acids (LC-n3 PUFAs) from seafood, to estimate the population proportion at risk for exceeding tolerable MeHg intake and not reaching adequate intake of PUFAs. Seafood consumption data was collected among women of childbearing age using a food frequency questionnaire. A database of mercury and fatty acids concentration in seafood was constructed. A Latin Hypercube simulation was used to calculate the intake of MeHg and LC n-3 PUFAs. Eleven percent of the population exceeded the MeHg reference dose of 0.1 mu g/kg bw/day, whereas only 44% reached an adequate PUFA intake. A small proportion (3.7%) exceeded the MeHg reference dose while at the same time did not reach an adequate PUFA intake. Furthermore, we simulated two scenarios in which seafood is consumed according to a general recommendation of three servings per week, whereof one serving of oily seafood. The first scenario included seafood with typically low MeHg concentrations (mean 0.056 and 0.027 mu g MeHg/g fish in lean and oily species, respectively), and the second included seafood typically high in MeHg concentrations (mean 0.50 and 0.26 mu g MeHg/g fish in lean and oily species, respectively). In the "high"scenario, almost 100% of the population exceeded the reference dose, whereas the corresponding proportion was only 5% in the "low" scenario. Overall, the results stress the importance of communicating species specific seafood consumption advisories for women of childbearing age in general and for pregnant women in particular, while at the same time encourage them to consume more seafood.

  • 49.
    Vrethem, Magnus
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Neurology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Neurology.
    Lindh, J
    Ryhov County Hospital, Sweden .
    Tondel, Martin
    Linköping University, Department of Clinical and Experimental Medicine, Occupational and Environmental Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Occupational and Environmental Medicine Center.
    Persson, B
    University of Gothenburg, Sweden .
    Dahle, Charlotte
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    IgA antibodies against tissue transglutaminase, endomysium and gliadin in idiopathic polyneuropathy2013In: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 127, no 2, p. 109-115Article in journal (Refereed)
    Abstract [en]

    Objectives To study the prevalence of antibodies of IgA class against tissue transglutaminase (tTG), endomysium (EMA) and gliadin (AGA) in patients with chronic idiopathic axonal polyneuropathy (CIAP) and to characterize the patients clinically and neurophysiologically. Methods Of 182 patients, 126 patients agreed to blood sampling. Sera were analysed by ELISAs detecting anti-tTG and AGA, whereas EMA was analysed by indirect immunofluorescence (IF) microscopy. Gastrointestinal symptoms were assessed by data from medical records and patient interviews. Results Nine of 126 patients (7%) were seropositive in at least one test (five with positive anti-tTG and/or EMA and four with positive AGA only). One patient with elevated levels of all specificities had laboratory signs of malabsorption and gastrointestinal complaints with abdominal pain and diarrhoea. Conclusions Elevated levels of IgA-AGA were slightly more frequent in patients with CIAP (4%) compared to 2.5% in 1866 healthy blood donors. Highly specific serological markers indicative of coeliac disease (CD) (anti-tTG and EMA) were somewhat more common in our patients with CIAP (4%) than expected from normal reference values and from studies of the prevalence of CD in the general population. Even though these findings may indicate a relationship, the aetiological importance is unclear.

  • 50.
    Wieslander, Gunilla
    et al.
    Uppsala University.
    Fabjan, Nina
    University of Ljubljana.
    Vogrincic, Maja
    University of Ljubljana.
    Kreft, Ivan
    University of Ljubljana.
    Janson, Christer
    Uppsala University.
    Spetz-Nystrom, Ulrike
    Uppsala University.
    Vombergar, Blanka
    Vocat College.
    Tagesson, Christer
    Linköping University, Department of Clinical and Experimental Medicine, Occupational and Environmental Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Occupational and Environmental Medicine Centre.
    Leanderson, Per
    Linköping University, Department of Clinical and Experimental Medicine, Occupational and Environmental Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Occupational and Environmental Medicine Centre.
    Norback, Dan
    Uppsala University.
    Eating Buckwheat Cookies Is Associated with the Reduction in Serum Levels of Myeloperoxidase and Cholesterol: A Double Blind Crossover Study in Day-Care Centre Staffs2011In: Tohoku journal of experimental medicine, ISSN 0040-8727, E-ISSN 1349-3329, Vol. 225, no 2, p. 123-130Article in journal (Refereed)
    Abstract [en]

    Buckwheat food is a good source of antioxidants, e.g. rutin, and other beneficial substances. Here we investigated the effects of the intake of common buckwheat (low rutin content) and tartary buckwheat cookies (high rutin content) on selected clinical markers. A double blind crossover study was performed among female day-care centre staffs (N = 62) from five day-care centres. Participants were randomly divided into two groups. The first group initially consumed four common buckwheat cookies per day (16.5 mg rutin equivalents/day) for two weeks, while the second group consumed four tartary buckwheat cookies per day (359.7 mg rutin equivalents/day). Then the groups switched their type of cookies and consumed them for another two weeks. We monitored selected clinical markers related to cardiovascular disease and lower airway inflammation, lung function, and subjective breathing difficulties in the staffs. Intake of tartary buckwheat cookies reduced the serum level of myeloperoxidase (MPO) by a factor 0.84 (p = 0.02). When grouping the two types of buckwheat cookies together, there was a reduction of total serum cholesterol (p andlt; 0.001) and HDL-cholesterol (p andlt; 0.001) during the study period, with improved lung vital capacity (p andlt; 0.001). The degree of reduction in total and HDL cholesterol levels was similar in staffs with low and high body mass index (cut off 25). In conclusion, intake of tartary buckwheat cookies with high level of the antioxidant rutin may reduce levels of MPO, an indicator of inflammation. Moreover, intake of both types of buckwheat cookies may lower cholesterol levels.

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