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  • 1.
    Bajramaj, Ermira
    et al.
    Malmo Univ, Sweden.
    Haggman-Henrikson, Birgitta
    Malmo Univ, Sweden; Umea Univ, Sweden.
    Dawson, Andreas
    Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Public Dental Health Care, Center for Oral Rehabilitation Norrköping. Region Östergötland, 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 Medicine and Health Sciences. Region Östergötland, 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 Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
    The Effect of Microdialysis Catheter Insertion on Glutamate and Serotonin Levels in Masseter Muscle in Patients with Myofascial Temporomandibular Disorders and Healthy Controls2019In: Diagnostics (Basel), ISSN 2075-4418, Vol. 9, no 1, article id 14Article in journal (Refereed)
    Abstract [en]

    Myofascial temporomandibular disorders (TMD) are the most common cause of chronic pain in the orofacial region. Microdialysis has been used to study metabolic changes in the human masseter muscle. The insertion of the microdialysis probe causes acute tissue trauma that could affect the metabolic milieu and thereby influence the results when comparing healthy subjects to those with TMD. This study aimed to investigate the levels of serotonin and glutamate during the acute tissue trauma period in healthy subjects and in patients with TMD. Microdialysis was carried out in 15 patients with TMD and 15 controls, and samples were collected every 20 min during a period of 140 min. No significant alterations of serotonin or glutamate were observed over the 2 h period for the healthy subjects. For the TMD group, a significant decrease in serotonin was observed over time (p amp;lt; 0.001), followed by a significant increase between 120 and 140 min (p amp;lt; 0.001). For glutamate, a significant reduction was observed at 40 min compared to baseline. The results showed that there was a spontaneous increase of serotonin 2 h after the insertion of the catheter in patients with TMD. In conclusion, the results showed that there are differences in the masseter muscle levels of serotonin and glutamate during acute nociception in patients with myofascial TMD compared to healthy subjects.

  • 2.
    Bäckryd, Emmanuel
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
    Edström, Sofia
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Gerdle, Björn
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, 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 Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
    Do fragments and glycosylated isoforms of alpha-1-antitrypsin in CSF mirror spinal pathophysiological mechanisms in chronic peripheral neuropathic pain? An exploratory, discovery phase study2018In: BMC Neurology, ISSN 1471-2377, E-ISSN 1471-2377, Vol. 18, article id 116Article in journal (Refereed)
    Abstract [en]

    Background: Post-translational modifications (PTMs) generate a tremendous protein diversity from the similar to 20,000 protein-coding genes of the human genome. In chronic pain conditions, exposure to pathological processes in the central nervous system could lead to disease-specific PTMs detectable in the cerebrospinal fluid (CSF). In a previous hypothesis-generating study, we reported that seven out of 260 CSF proteins highly discriminated between neuropathic pain patients and healthy controls: one isoform of angiotensinogen (AG), two isoforms of alpha-1-antitrypsin (AT), three isoforms of haptoglobin (HG), and one isoform of pigment epithelium-derived factor (PEDF). The present study had three aims: (1) To examine the multivariate inter-correlations between all identified isoforms of these seven proteins; (2) Based on the results of the first aim, to characterize PTMs in a subset of interesting proteins; (3) To regress clinical pain data using the 260 proteins as predictors, thereby testing the hypothesis that the above-mentioned seven discriminating proteins and/or the characterized isoforms/fragments of aim (2) would be among the proteins having the highest predictive power for clinical pain data. Methods: CSF samples from 11 neuropathic pain patients and 11 healthy controls were used for biochemical analysis of protein isoforms. PTM characterization was performed using enzymatic reaction assay and mass spectrometry. Multivariate data analysis (principal component analysis and orthogonal partial least square regression) was applied on the quantified protein isoforms. Results: We identified 5 isoforms of AG, 18 isoforms of AT, 5 isoforms of HG, and 5 isoforms of PEDF. Fragments and glycosylated isoforms of AT were studied in depth. When regressing the pain intensity data of patients, three isoforms of AT, two isoforms of PEDF, and one isoform of angiotensinogen "reappeared" as major results, i.e., they were major findings both when comparing patients with healthy controls and when regressing pain intensity in patients. Conclusions: Altered levels of fragments and/or glycosylated isoforms of alpha-1-antitrypsin might mirror pathophysiological processes in the spinal cord of neuropathic pain patients. In particular, we suggest that a putative disease-specific combination of the levels of two different N-truncated fragments of alpha-1-antitrypsin might be interesting for future CSF and/or plasma biomarker investigations in chronic neuropathic pain.

  • 3.
    Bäckryd, Emmanuel
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, 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, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center. Region Östergötland, Heart and Medicine Center, Occupational and Environmental Medicine Center.
    Carlsson, Anders K
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
    Olausson, Patrik
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, 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 Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
    Multivariate proteomic analysis of the cerebrospinal fluid of patients with peripheral neuropathic pain and healthy controls: a hypothesis-generating pilot study2015In: Journal of Pain Research, ISSN 1178-7090, E-ISSN 1178-7090, Vol. 8, p. 321-333Article in journal (Refereed)
    Abstract [en]

    Pain medicine lacks objective biomarkers to guide diagnosis and treatment. Combining two-dimensional gel proteomics with multivariate data analysis by projection, we exploratively analyzed the cerebrospinal fluid of eleven patients with severe peripheral neuropathic pain due to trauma and/or surgery refractory to conventional treatment and eleven healthy controls. Using orthogonal partial least squares discriminant analysis, we identified a panel of 36 proteins highly discriminating between the two groups. Due to a possible confounding effect of age, a new model with age as outcome variable was computed for patients (n=11), and four out of 36 protein spots were excluded due to a probable influence of age. Of the 32 remaining proteins, the following seven had the highest discriminatory power between the two groups: an isoform of angiotensinogen (upregulated in patients), two isoforms of alpha-1-antitrypsin (downregulated in patients), three isoforms of haptoglobin (upregulated in patients), and one isoform of pigment epithelium-derived factor (downregulated in patients). It has recently been hypothesized that the renin–angiotensin system may play a role in the pathophysiology of neuropathic pain, and a clinical trial of an angiotensin II receptor antagonist was recently published. It is noteworthy that when searching for neuropathic pain biomarkers with a purely explorative methodology, it was indeed a renin–angiotensin system protein that had the highest discriminatory power between patients and controls in the present study. The results from this hypothesis-generating pilot study have to be confirmed in larger, hypothesis-driven studies with age-matched controls, but the present study illustrates the fruitfulness of combining proteomics with multivariate data analysis in hypothesis-generating pain biomarker studies in humans.

  • 4.
    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.

  • 5.
    Bäckryd, Emmanuel
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, 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 Medicine and Health Sciences. Region Östergötland, 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 Medicine and Health Sciences. Region Östergötland, 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 Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
    Plasma pro-inflammatory markers in chronic neuropathic pain: A multivariate, comparative, cross-sectional pilot study2016In: Scandinavian Journal of Pain, ISSN 1877-8860, E-ISSN 1877-8879, no 10, p. 1-5Article in journal (Refereed)
    Abstract [en]

    Background: Caused by a lesion or disease of the somatosensory system, neuropathic pain is notoriously difficult to treat with conventional analgesics. It has been suggested that inflammatory cytokines play a role in the development and maintenance of neuropathic pain. But human studies of these substances are relatively few and partly contradictory. Objectives: To simultaneously investigate the plasma levels of chemokine interleukin 8 (IL-8) and the cytokines IL-6, IL-1, and Granulocyte macrophage colony-stimulating factor (GM-CSF) in patients with peripheral neuropathic pain (most of whom due to failed back surgery syndrome) (n = 14) compared to controls (n = 17). Results: IL-6 was significantly higher in patients than in controls (0.92 ± 0.12 pg/ml vs. 0.57 ± 0.08 pg/ml, p = 0.012). IL-1, IL-8, and GM-CSF levels did not differ between the two groups. A multivariate analysis showed a tendency for patients also to have higher GM-CSF plasma levels than controls. Conclusions: This study found an increased level of IL-6 in plasma in patients with neuropathic pain, but not for the other pro-inflammatory substances investigated. There are several possible confounders not registered or controlled for in this and other studies of neuropathic pain. Implications: Larger studies that take several possible confounders into consideration are needed to further investigate the levels of plasma cytokines in different pain conditions. © 2015 Scandinavian Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

  • 6.
    Christidis, Nikolaos
    et al.
    Karolinska Institute, Sweden; SCON, Sweden.
    Ghafouri, Bijar
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center. Region Östergötland, Heart and Medicine Center, Occupational and Environmental Medicine Center.
    Larsson, Anette
    University of Gothenburg, Sweden; .
    Palstam, Annie
    University of Gothenburg, Sweden.
    Mannerkorpi, Kaisa
    University of Gothenburg, Sweden; .
    Bileviciute-Ljungar, Indre
    Karolinska Institute, Sweden.
    Lofgren, Monika
    Karolinska Institute, Sweden.
    Bjersing, Jan
    University of Gothenburg, Sweden.
    Kosek, Eva
    Karolinska Institute, Sweden; Stockholm Spine Centre, Sweden.
    Gerdle, Björn
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
    Ernberg, Malin
    Karolinska Institute, Sweden; SCON, Sweden.
    Comparison of the Levels of Pro-Inflammatory Cytokines Released in the Vastus Lateralis Muscle of Patients with Fibromyalgia and Healthy Controls during Contractions of the Quadriceps Muscle - A Microdialysis Study2015In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 10, no 12, p. e0143856-Article in journal (Refereed)
    Abstract [en]

    Objective Fibromyalgia is associated with central hyperexcitability, but it is suggested that peripheral input is important to maintain central hyperexcitability. The primary aim was to investigate the levels of pro-inflammatory cytokines released in the vastus lateralis muscle during repetitive dynamic contractions of the quadriceps muscle in patients with fibromyalgia and healthy controls. Secondarily, to investigate if the levels of pro-inflammatory cytokines were correlated with pain or fatigue during these repetitive dynamic contractions. Material and Methods 32 women with fibromyalgia and 32 healthy women (controls) participated in a 4 hour microdialysis session, to sample IL-1 beta, IL-6, IL-8, and TNF from the most painful point of the vastus lateralis muscle before, during and after 20 minutes of repeated dynamic contractions. Pain (visual analogue scale; 0-100) and fatigue Borgs Rating of Perceived Exertion Scale; 6-20) were assessed before and during the entire microdialysis session. Results The repetitive dynamic contractions increased pain in the patients with fibromyalgia (P &lt; .001) and induced fatigue in both groups (P &lt; .001). Perceived fatigue was significantly higher among patients with fibromyalgia than controls (P &lt; .001). The levels of IL-1 beta did not change during contractions in either group. The levels of TNF did not change during contractions in patients with fibromyalgia, but increased in controls (P &lt; .001) and were significantly higher compared to patients with fibromyalgia (P = .033). The levels of IL-6 and IL-8 increased in both groups alike during and after contractions (Ps &lt; .001). There were no correlations between pain or fatigue and cytokine levels after contractions. Conclusion There were no differences between patients with fibromyalgia and controls in release of pro-inflammatory cytokines, and no correlations between levels of pro-inflammatory cytokines and pain or fatigue. Thus, this study indicates that IL-1 beta, IL-6, IL-8, and TNF do not seem to play an important role in maintenance of muscle pain in fibromyalgia.

  • 7.
    Dawson, Andreas
    et al.
    Malmö University, Sweden.
    Ghafouri, Bijar
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center. Region Östergötland, 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 Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
    List, Thomas
    Malmö University, Sweden; Skåne University Hospital, Sweden.
    Svensson, Peter
    Aarhus University, Denmark.
    Ernberg, Malin
    Karolinska Institute, Sweden; Aarhus University Hospital, Denmark.
    Effects of Experimental Tooth Clenching on Pain and Intramuscular Release of 5-HT and Glutamate in Patients With Myofascial TMD2015In: The Clinical Journal of Pain, ISSN 0749-8047, E-ISSN 1536-5409, Vol. 31, no 8, p. 740-749Article in journal (Refereed)
    Abstract [en]

    Objectives: It has been suggested that tooth clenching may be associated with local metabolic changes, and is a risk factor for myofascial temporomandibular disorders (M-TMD). This study investigated the effects of experimental tooth clenching on the levels of 5-HT, glutamate, pyruvate, and lactate, as well as on blood flow and pain intensity, in the masseter muscles of M-TMD patients. Methods: Fifteen patients with M-TMD and 15 pain-free controls participated. Intramuscular microdialysis was performed to collect 5-HT, glutamate, pyruvate, and lactate and to assess blood flow. Two hours after the insertion of a microdialysis catheter, participants performed a 20-minute repetitive tooth clenching task (50% of maximal voluntary contraction). Pain intensity was measured throughout. Results: A significant effect of group (P less than 0.01), but not of time, was observed on 5-HT levels and blood flow. No significant effects of time or group occurred on glutamate, pyruvate, or lactate levels. Time and group had significant main effects on pain intensity (P less than 0.05 and less than 0.001). No significant correlations were identified between: (1) 5-HT, glutamate, and pain intensity; or between (2) pyruvate, lactate, and blood flow. Discussion: This experimental tooth clenching model increased jaw muscle pain levels in M-TMD patients and evoked low levels of jaw muscle pain in controls. M-TMD patients had significantly higher levels of 5-HT than controls and significantly lower blood flow. These 2 factors may facilitate the release of other algesic substances that may cause pain.

  • 8.
    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.

  • 9.
    Dawson, Andreas
    et al.
    Region Östergötland, Public Dental Health Care. Malmö University, Sweden; Karolinska Institute, Sweden; Malmö University, Sweden; Aarhus University, Denmark.
    Stensson, Niclas
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Ghafouri, Bijar
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, 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 Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
    List, Thomas
    Malmö University, Sweden; Skåne University Hospital, Sweden; Karolinska Institute, Sweden; Malmö University, Sweden; Aarhus University, Denmark.
    Svensson, Peter
    Aarhus University, Denmark; Aarhus University Hospital, Denmark; Karolinska Institute, Sweden; Karolinska Institute, Sweden; Malmö University, Sweden; Aarhus University, Denmark.
    Ernberg, Malin
    Karolinska Institute, Sweden; Karolinska Institute, Sweden; Malmö University, Sweden; Aarhus University, Denmark.
    Dopamine in plasma - a biomarker for myofascial TMD pain?2016In: Journal of Headache and Pain, ISSN 1129-2369, E-ISSN 1129-2377, Vol. 17, no 65Article in journal (Refereed)
    Abstract [en]

    Background: Dopaminergic pathways could be involved in the pathophysiology of myofascial temporomandibular disorders (M-TMD). This study investigated plasma levels of dopamine and serotonin (5-HT) in patients with M-TMD and in healthy subjects. Methods: Fifteen patients with M-TMD and 15 age-and sex-matched healthy subjects participated. The patients had received an M-TMD diagnosis according to the Research Diagnostic Criteria for TMD. Perceived mental stress, pain intensity (0-100-mm visual analogue scale), and pressure pain thresholds (PPT, kPa) over the masseter muscles were assessed; a venous blood sample was taken. Results: Dopamine in plasma differed significantly between patients with M-TMD (4.98 +/- 2.55 nM) and healthy controls (2.73 +/- 1.24 nM; P amp;lt; 0.01). No significant difference in plasma 5-HT was observed between the groups (P = 0.75). Patients reported significantly higher pain intensities (P amp;lt; 0.001) and had lower PPTs (P amp;lt; 0.01) compared with the healthy controls. Importantly, dopamine in plasma correlated significantly with present pain intensity (r = 0.53, n = 14, P amp;lt; 0.05) and perceived mental stress (r = 0.34, n = 28, P amp;lt; 0.05). Conclusions: The results suggest that peripheral dopamine might be involved in modulating peripheral pain. This finding, in addition to reports in other studies, suggests that dopaminergic pathways could be implicated in the pathophysiology of M-TMD but also in other chronic pain conditions. More research is warranted to elucidate the role of peripheral dopamine in the pathophysiology of chronic pain.

  • 10.
    Djerf Svenningsson, Emelie
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Oncology. Linköping University, Faculty of Health Sciences.
    Olausson, Patrik
    Linköping University, Department of Medical and Health Sciences, Rehabilitation 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, Sinnescentrum, Pain and Rehabilitation Centre.
    Stål, Olle
    Linköping University, Department of Clinical and Experimental Medicine, Oncology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology UHL.
    Hallbeck, Anna-Lotta
    Linköping University, Department of Clinical and Experimental Medicine, Oncology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology UHL.
    Walz, Thomas
    Linköping University, Department of Clinical and Experimental Medicine, Oncology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology UHL.
    Resistance to gefitinib in malignant melanoma cells is related to increased expression of Met and the insulin receptor and sustained Akt signaling2012Manuscript (preprint) (Other academic)
    Abstract [en]

    Background: Acquired resistance to cancer therapy, including targeted therapies such as epidermal growth factor receptor (ErbB) tyrosine kinase inhibitors (TKIs), constitutes a major clinical problem in treating patients with malignant disease. Several drug resistance mechanisms for ErbB1 TKIs involving abnormal activation of growth factor receptors or activation of intracellular signaling pathways have been discovered. ErbB TKIs have recently been shown to inhibit growth in melanoma cells. This study was undertaken to develop a gefitinib-resistant melanoma cell line in order to find any resistance mechanism to gefitinib in melanoma cells lacking activating mutation in BRAF or NRAS.

    Material and methods: A malignant melanoma cell line (RaH5) was made resistant to the ErbB1 TKI gefitinib by continuous culture with stepwise increasing concentrations of the drug up to 10 μM. The phosphorylation status of 42 different human receptor tyrosine kinases was screened in a protein array in resistant (RaH5ZDR) and wild-type RaH5 cells treated with or without gefitinib. The PI3K, MAPK and Stat3 signaling pathways were studied in an analogous way by Western blot analysis; 2-D gel electrophoresis was performed to determine other potential proteins involved in gefitinib resistance in RaH5 cells. In addition, the effect of the pan-ErbB TKI canertinib on gefitinib-resistant cells was investigated.

    Results: Protein array experiments showed that only Met and the insulin receptor (IR) exhibited substantially increased activation in RaH5ZDR cells as compared to their nonresistant counterparts. Interestingly, following gefitinib treatment ErbB2 and ErbB3 receptor signaling in resistant cells were equally well suppressed as in non-resistant cells. However, downstream Akt and Erk1/2 phosphorylation was inhibited to a greater extent in non-resistant RaH5 cells.

    Conclusion: Resistance to gefitinib in RaH5 cells appears to be related to an increased expression of Met and IR and linked to a more persistent signaling through Akt and Erk1/2. However, additional studies are required to further elucidate the resistance to gefitinib in our experimental system.

  • 11.
    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.

  • 12.
    Ernberg, M.
    et al.
    Karolinska Inst, Sweden; SCON, Sweden.
    Christidis, N.
    Karolinska Inst, Sweden; SCON, Sweden.
    Ghafouri, Bijar
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
    Bileviciute-Ljungar, I.
    Karolinska Inst, Sweden; Danderyd Hosp, Sweden.
    Lofgren, M.
    Karolinska Inst, Sweden; Danderyd Hosp, Sweden.
    Bjersing, J.
    Univ Gothenburg, Sweden.
    Palstam, A.
    Univ Gothenburg, Sweden.
    Larsson, A.
    Univ Gothenburg, Sweden.
    Mannerkorpi, K.
    Univ Gothenburg, Sweden.
    Gerdle, Björn
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
    Kosek, E.
    Karolinska Inst, Sweden; Stockholm Spine Ctr, Sweden.
    Plasma Cytokine Levels in Fibromyalgia and Their Response to 15 Weeks of Progressive Resistance Exercise or Relaxation Therapy2018In: Mediators of Inflammation, ISSN 0962-9351, E-ISSN 1466-1861, article id 3985154Article in journal (Refereed)
    Abstract [en]

    The aims of this study were to compare circulating cytokines between FM and healthy controls and to investigate the effect on cytokine levels by 15 weeks of progressive resistance exercise or relaxation therapy in FM. Baseline plasma cytokine levels and clinical data were analyzed in 125 women with FM and 130 age-matched healthy women. The FM women were then randomized to progressive resistance exercise (n = 49) or relaxation (n = 43). Baseline IL-2, IL-6, TNF-alpha, IP-10, and eotaxin were higher in FM than in healthy controls (P amp;lt; 0.041), whereas IL-beta was lower (P amp;lt; 0.001). There were weak correlations between cytokine levels and clinical variables. After both interventions, IL-1ra had increased (P=0.004), while IL-1 beta had increased in the relaxation group (P = 0.002). Changes of IFN-gamma, IL-2, IL-4, IL-6, IL-8, and IL-17A were weakly correlated with changes of PPT, but there were no significant correlations between changes of cytokine and changes in other clinical variables. The elevated plasma levels of several cytokines supports the hypothesis that chronic systemic inflammation may underlie the pathophysiology of FM even if the relation to clinical variables was weak. However, 15 weeks of resistance exercise, as performed in this study, did not show any anti-inflammatory effect on neither FM symptoms nor clinical and functional variables.

  • 13.
    Ernberg, Malin
    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 Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
    Bileviciute-Ljungar, Indre
    Karolinska Institute, Sweden; Danderyd Hospital, Sweden.
    Löfgren, Monika
    Karolinska Institute, Sweden; Danderyd Hospital, Sweden.
    Larsson, Anette
    University of Gothenburg, Sweden; University of Gothenburg, Sweden.
    Palstam, Annie
    University of Gothenburg, Sweden.
    Bjersing, Jan
    University of Gothenburg, Sweden.
    Mannerkorpi, Kaisa
    University of Gothenburg, Sweden; University of Gothenburg, Sweden.
    Kosek, Eva
    Karolinska Institute, Sweden; Stockholm Spine Centre, Sweden.
    Gerdle, Björn
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
    Effects of 15 weeks of resistance exercise on pro-inflammatory cytokine levels in the vastus lateralis muscle of patients with fibromyalgia2016In: Arthritis Research & Therapy, ISSN 1478-6354, E-ISSN 1478-6362, Vol. 18, no 137Article in journal (Refereed)
    Abstract [en]

    Background: This study aimed at investigating the effect of a resistance exercise intervention on the interstitial muscle levels of pro-inflammatory cytokines in fibromyalgia (FMS) and healthy controls (CON). Methods: Twenty-four female patients with FMS (54 +/- 8 years) and 27 female CON (54 +/- 9 years) were subjected to intramuscular microdialysis of the most painful vastus lateralis muscle before and after 15 weeks of progressive resistance exercise twice per week. Baseline dialysates were sampled in the resting muscle 140 min after insertion of the microdialysis catheter. The participants then performed repetitive dynamic contractions (knee extension) for 20 min, followed by 60 min rest. Pain intensity was assessed with a 0-100 mm visual analogue scale (VAS), and fatigue was assessed with Borgs RPE throughout microdialysis. Dialysates were sampled every 20 min and analyzed with Luminex for interleukin (IL)-1 beta, tumor necrosis factor (TNF) alpha, IL-6, and IL-8. Results: At both sessions and for both groups the dynamic contractions increased pain (P amp;lt; 0.012) and fatigue (P amp;lt; 0.001). The levels of TNF were lower in the FMS group than the CON group at both sessions (P amp;lt; 0.05), but none of the other cytokines differed between the groups. IL-6 and IL-8 increased after the dynamic contractions in both groups (P amp;lt; 0.010), while TNF increased only in CON (P amp;lt; 0.05) and IL-1 beta did not change. Overall pain intensity was reduced after the 15 weeks of resistance exercise in FMS (P amp;lt; 0.05), but there was no changes in fatigue or cytokine levels. Conclusion: Progressive resistance exercise for 15 weeks did not affect the interstitial levels of IL-1 beta, TNF, IL-6, and IL-8 in the vastus lateralis muscle of FMS patients or CON.

  • 14.
    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.

  • 15.
    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.

  • 16.
    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.

  • 17.
    Gerdle, Björn
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
    Ernberg, Malin
    Karolinska Institute, Department of Dental Medicine, Section of Orofacial Pain and Jaw Function / Scandinavian Centre for Orofacial Neuroscience (SCON), Stockholm, Sweden.
    Mannerkorpi, Kaisa
    Section of Physiotherapy, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden / University of Gothenburg Centre for Person-Centred Care (GPCC), Sahlgrenska Academy, Gothenburg, Sweden.
    Larsson, Britt
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
    Kosek, Eva
    Department of Clinical Neuroscience and Osher Centre for Integrative Medicine, Karolinska Institute, Stockholm, Sweden.
    Christidis, Nikolaos
    Karolinska Institute, Department of Dental Medicine, Section of Orofacial Pain and Jaw Function / Scandinavian Centre for Orofacial Neuroscience (SCON), Stockholm, Sweden.
    Ghafouri, Bijar
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
    Increased Interstitial Concentrations of Glutamate and Pyruvate in Vastus Lateralis of Women with Fibromyalgia Syndrome Are Normalized after an Exercise Intervention: a Case-Control Study2016In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 11, no 10, p. 14article id e0162010Article in journal (Refereed)
    Abstract [en]

    Background Fibromyalgia syndrome (FMS) is associated with central alterations, but controversies exist regarding the presence and role of peripheral factors. Microdialysis (MD) can be used in vivo to study muscle alterations in FMS. Furthermore for chronic pain conditions such as FMS, the mechanisms for the positive effects of exercise are unclear. This study investigates the interstitial concentrations of algesics and metabolites in the vastus lateralis muscle of 29 women with FMS and 28 healthy women before and after an exercise intervention. Methods All the participants went through a clinical examination and completed a questionnaire. In addition, their pressure pain thresholds (PPTs) in their upper and lower extremities were determined. For both groups, MD was conducted in the vastus lateralis muscle before and after a 15-week exercise intervention of mainly resistance training of the lower limbs. Muscle blood flow and interstitial muscle concentrations of lactate, pyruvate, glutamate, glucose, and glycerol were determined. Results FMS was associated with significantly increased interstitial concentrations of glutamate, pyruvate, and lactate. After the exercise intervention, the FMS group exhibited significant decreases in pain intensity and in mean interstitial concentrations of glutamate, pyruvate, and glucose. The decrease in pain intensity in FMS correlated significantly with the decreases in pyruvate and glucose. In addition, the FMS group increased their strength and endurance. Conclusion This study supports the suggestion that peripheral metabolic and algesic muscle alterations are present in FMS patients and that these alterations contribute to pain. After an exercise intervention, alterations normalized, pain intensity decreased (but not abolished), and strength and endurance improved, all findings that suggest the effects of exercise are partially peripheral.

  • 18.
    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.

  • 19.
    Gerdle, Björn
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, 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 Medicine and Health Sciences. Region Östergötland, 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 Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
    Bäckryd, Emmanuel
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
    Gordh, Torsten
    Uppsala University, Sweden.
    Signs of ongoing inflammation in female patients with chronic widespread pain A multivariate, explorative, cross-sectional study of blood samples2017In: Medicine (Baltimore, Md.), ISSN 0025-7974, E-ISSN 1536-5964, Vol. 96, no 9, article id e6130Article in journal (Refereed)
    Abstract [en]

    This cross-sectional study investigates the plasma inflammatory profile of chronic widespread pain CWP) patients compared to healthy controls CON). Rather than analyzing a relatively few substances at a time, we used a new multiplex proximity extension assay PEA) panel that enabled the simultaneous analysis of 92 inflammation-related proteins, mainly cytokines and chemokines. Seventeen women with CWP and 21 female CON participated and a venous blood sample was drawn from all subjects. Pain intensity and pain thresholds for pressure, heat, and cold were registered. A PEA panel 92 proteins) was used to analyze the blood samples. Multivariate data analysis by projection was used in the statistical analyses. Eleven proteins significantly differentiated the CON and CWP subjects R-2=0.58, Q(2)=0.37, analysis of variance of cross-validated predictive residuals P=0.006). It was not possible to significantly regress pain thresholds within each group CON or CWP). Positive significant correlations existed between several proteins and pain intensities in CWP, but the model reliability of the regression was poor. CWP was associated with systemic low-grade inflammation. Larger studies are needed to confirm the results and to investigate which alterations are condition-specific and which are common across chronic pain conditions. The presence of inflammation could promote the spreading of pain, a hallmark sign of CWP. As it has been suggested that prevalent comorbidities to pain (e.g., depression and anxiety, poor sleep, and tiredness) also are associated with inflammation, it will be important to determine whether inflammation may be a common mediator.

  • 20.
    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.

  • 21.
    Ghafouri, Bijar
    Linköping University, Department of Molecular and Clinical Medicine, Occupational and Environmental Medicine. Linköping University, Faculty of Health Sciences.
    Proteomics of the upper airways: studies on a new lipopolysaccharide-binding protein, PLUNC2005Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    There is now significant interest in identifying, quantifying and characterizing the human proteome, and new powerful techniques (proteomics) have evolved to deal with this giant task. In the present study, proteomics have been applied for the first time to map the proteins of the upper airways. The protein contents of human nasal fluid (NLF) and saliva were analysed using two-dimensional polyacrylamide gel electrophoresis (2-D PAGE) and the proteins were identified by peptide mass fingerprinting using matrix assisted laser desorptioniionization time of night mass spectrometry (MALDI-TOF MS) or by amino acid sequencing using electrospray ionization tandem mass spectrometry (ESI- MS/MS). More than 100 proteins were identified and protein maps of nasal fluid and saliva were thus established. Of particular interest was the identification of a new lipopolysaccharide (LPS)-binding protein, PLUNC (palate lung and nasal epithelial clone), which was shown to be the only protein in NLF that binds to LPS. PLUNC was characterized as multiple isoforms (Mr/p1: 27/5.1, 26/5.2, 25/5.3, 27.5/5.1, 27/5.2, 26/5.3, 25.1/5.5 and 24.8/5.4), and several of these isoforms were demonstrated to be sialylated. Notably, decreased levels of PLUNC were found in NLF of (i) smokers, (ii) epoxy workers with airway irritation, and (iii) patients with seasonal allergic rhinitis (SAR) during allergy season. In addition, the levels of von Ebner's gland protein, α1-antitrypsin, cystatin S, Clara cell protein 16 and lipocortin-1 were altered, either in smokers or SAR patients or both. One previously unidentified NLF protein was found in SAR patients during allergy season but not before season: this protein was identified as eosinophil lysophospholipase. Many of these proteins were post-translationally modified by glycosylation (PLUNC, α1-antitrypsin, von Ebner's gland protein), phosphorylation (cystatin S), acetylation (eosinophil lysophospholipase), or truncation (lipocortin-1). Altogether, these findings illustrate the potential use of proteomics for identifying new markers of upper airway inflammation and for revealing structural details of such markers. The findings also indicate that allergic inflammation in the nasal mucosa is associated with decreased nasal fluid levels of the endogenous proteinase inhibitors, cystatin S and von Ebner's gland protein, and of the new irritation marker, PLUNC. Further studies are required to explore the possibility that PLUNC plays an important part in microbial  recognition and that this function is impaired after exposure to airway irritants and during upper airway inflammation.

    List of papers
    1. Newly identified proteins in human nasal lavage fluid from non-smokers and smokers using two-dimensional gel electrophoresis and peptide mass fingerprinting
    Open this publication in new window or tab >>Newly identified proteins in human nasal lavage fluid from non-smokers and smokers using two-dimensional gel electrophoresis and peptide mass fingerprinting
    2002 (English)In: Proteomics, ISSN 1615-9853, E-ISSN 1615-9861, Vol. 2, no 1, p. 112-120Article in journal (Refereed) Published
    Abstract [en]

    Human nasal lavage fluids (NLFs) were analyzed with two-dimensional gel electrophoresis (2-DE) and proteins were identified with peptide mass fingerprinting using matrix-assisted laser desoption/ionization time of flight mass spectrometry. In some cases, the identification was verified by analysis of post-source decay fragmentation spectra. Many of the identified proteins were new forms or fragments of previously found proteins (e.g. albumin, lactoferrin, cystatin, calgranulin, von Ebners gland protein and palate lung nasal epithelium clone), while others were proteins that have previously been indicated by 2-DE image matching or immunoblots (e.g. apolipoprotein AI, lysozyme C, and Clara cell secretory protein). Some new proteins, not shown before in 2-DE patterns of NLF were also found, e.g. mammaglobin B, 2-microglobulin and immunoglobulin J chain. Of the identified NLF proteins many appear to be involved in inflammatory and immune responses. A study was therefore conducted to investigate if the levels of these proteins were changed in smokers compared to nonsmokers. It was found that NLF from smokers contained decreased levels of Clara cell secretory protein, and increased proportions of a truncated variant of lipocortin-1, three acidic forms of α1-antitrypsin, and one phosphorylated form of cystatin S. Furthermore, NLF from smokers contained increased proportions of a new variant of palate lung nasal epithelium clone (PLUNC), a recently identified airway irritation marker. The results demonstrate that 2-DE of NLF may be used to assess alterations of proteins or post-translationally modified proteins in smokers. Clara cell secretory protein (CC 16, CC 10) and lipocortin-1 are two anti-inflammatory, phospholipase A2 inhibitory proteins, and α1-antitrypsin and cystatin S are two proteinase inhibitors. Changed levels of these proteins may therefore be of importance to the airway inflammation caused by smoking. The results also support the notion that PLUNC is involved in inflammatory responses in the upper airways.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-26518 (URN)10.1002/1615-9861(200201)2:1<112::AID-PROT112>3.0.CO;2-N (DOI)11076 (Local ID)11076 (Archive number)11076 (OAI)
    Available from: 2009-10-08 Created: 2009-10-08 Last updated: 2017-12-13Bibliographically approved
    2. Mapping of proteins in human saliva using two-dimensional gel electrophoresis and peptide mass fingerprinting
    Open this publication in new window or tab >>Mapping of proteins in human saliva using two-dimensional gel electrophoresis and peptide mass fingerprinting
    2003 (English)In: Proteomics, ISSN 1615-9853, E-ISSN 1615-9861, Vol. 3, no 6, p. 1003-1015Article in journal (Refereed) Published
    Abstract [en]

    Human saliva contains a large number of proteins that can be used for diagnosis and are of great potential in clinical and epidemiological research. The aim of this work was to map the proteins in saliva by two-dimensional gel electrophoresis (2-DE), and to identify abundant proteins by peptide mass fingerprinting using trypsin cleavage and matrix-assisted laser desorption/ionization-time of flight-mass spectrometry analysis. One hundred proteins were identified representing 20 different identities according to accession numbers. Abundant proteins expressed in different forms were: α-amylase, immunoglobulin A, prolactin-inducible protein, zinc-α2-glycoprotein and cystatins (S, SA, D and SN). Other proteins found were interleukin-1 receptor antagonist, von Ebner’s gland protein (lipocalin-1) and calgranulin A and B (S100A8 and A9). Furthermore, apolipoprotein A-I, β2-microglobulin, glutathione S-transferase P and fatty acid-binding protein were also identified. Our results show that human saliva contains a large number of proteins that are involved in inflammatory and immune responses. The 2-DE protein map constructed opens the possibility to investigate protein changes associated with disease processes.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-26469 (URN)10.1002/pmic.200300426 (DOI)11020 (Local ID)11020 (Archive number)11020 (OAI)
    Available from: 2009-10-08 Created: 2009-10-08 Last updated: 2017-12-13Bibliographically approved
    3. PLUNC (palate, lung and nasal epithelial clone) proteins in human nasal lavage fluid
    Open this publication in new window or tab >>PLUNC (palate, lung and nasal epithelial clone) proteins in human nasal lavage fluid
    Show others...
    2003 (English)In: Biochemical Society Transactions, ISSN 0300-5127, E-ISSN 1470-8752, Vol. 31, no 4, p. 810-814Article in journal (Refereed) Published
    Abstract [en]

    PLUNC (palate, lung and nasal epithelial clone) is a newly discovered gene that is expressed in the upper respiratory tract and is suggested to be of importance in host defence against bacteria. We have identified two forms of the PLUNC protein in human nasal lavage fluid (NLF) using two-dimensional gel electrophoresis (2-DE) and MS. The apparent molecular masses and isoelectric points of these forms are 24.8 kDa/pI 5.4 and 25.1 kDa/pI 5.5. Notably, the 24.8 kDa/pI 5.4 form of PLUNC is an abundant protein in the 2-DE protein patterns of NLF from healthy subjects. Decreased levels of PLUNC were found in NLF from smokers and workers exposed to reactive epoxy chemicals, indicating that long-term exposure to airway irritants impairs the production of PLUNC in the upper respiratory tract. We have also investigated the presence of lipopolysaccharide (LPS)-binding proteins in NLF. Five proteins were found to adsorb to a LPS-coated surface; two of these proteins correspond to the two PLUNC forms, as judged by 2-DE pattern matching. For comparison, human saliva was found to contain a set of LPS-binding proteins with similar 2-DE spot positions (the same pIs but somewhat lower apparent molecular masses of 20 kDa). These results indicate that PLUNC may be a new marker of airway inflammation and may play a part in the innate immune response, and that human saliva contains yet other members of the family of LPS-binding proteins.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-26470 (URN)10.1042/BST0310810 (DOI)11021 (Local ID)11021 (Archive number)11021 (OAI)
    Available from: 2009-10-08 Created: 2009-10-08 Last updated: 2017-12-13Bibliographically approved
    4. PLUNC in human nasal lavage fluid: multiple isoforms that bind to lipopolysaccharide
    Open this publication in new window or tab >>PLUNC in human nasal lavage fluid: multiple isoforms that bind to lipopolysaccharide
    2004 (English)In: Biochimica et Biophysica Acta - Proteins and Proteomics, ISSN 1570-9639, E-ISSN 1878-1454, Vol. 1699, no 1-2, p. 57-63Article in journal (Refereed) Published
    Abstract [en]

    Here, we demonstrate the presence of multiple isoforms of palate lung nasal epithelial clone (PLUNC) in human nasal lavage fluid (NLF). Eight isoforms were separated by two-dimensional gel electrophoresis (2-DE), and peptide mapping of the proteins was performed using MALDI-TOF MS (matrix assisted laser desorption/ionization time of flight mass spectrometry) of tryptic and asparginase cleavages. The identification was verified by amino acid sequencing after analysis of collision-induced dissociation (CID) fragmentation spectra with nanoelectrospray MS/MS. One isoform showed an electrophoretic mobility shift after N-glycosidase treatment, indicating that at least one of the PLUNC isoforms is glycosylated. We also demonstrate that PLUNC in NLF binds to lipopolysaccharide (LPS) in vitro; indeed, out of all proteins present in NLF only the PLUNC isoforms were found to adsorb to an LPS-coated surface. These results show that PLUNC is expressed as multiple LPS-binding isoforms in human NLF. The possibility that PLUNC may play a role in the innate immune response of the upper airways is inferred.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-22261 (URN)10.1016/j.bbapap.2004.01.001 (DOI)1434 (Local ID)1434 (Archive number)1434 (OAI)
    Available from: 2009-10-07 Created: 2009-10-07 Last updated: 2017-12-13Bibliographically approved
    5. Comparative proteomics of nasal fluid in seasonal allergic rhinitis
    Open this publication in new window or tab >>Comparative proteomics of nasal fluid in seasonal allergic rhinitis
    Show others...
    2006 (English)In: Journal of Proteome Research, ISSN 1535-3893, E-ISSN 1535-3907, Vol. 5, no 2, p. 330-338Article in journal (Refereed) Published
    Abstract [en]

    A comparative proteomic approach was applied to examine nasal lavage fluid (NLF) from patients with seasonal allergic rhinitis (SAR, n = 6) and healthy subjects (controls, n = 5). NLF samples were taken both before allergy (pollen) season and during season, and proteins were analyzed by two-dimensional gel electrophoresis (2-DE) and matrix assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) after tryptic cleavage. Twenty proteins were selected and quantified. During allergy season, the levels of six sialylated isoforms of PLUNC (palate lung nasal epithelial clone) were lower in SAR patients than controls, as were the levels of six isoforms of von Ebner's gland protein (VEGP), including a previously undescribed form with N-linked glycosylation, and of cystatin S. PLUNC is a new innate immunity protein and VEGP and cystatin S are two endogenous proteinase inhibitors. By contrast, the levels of an acidic form of alpha-1-antitrypsin were higher in SAR patients than controls. One previously unidentified NLF protein was found in all samples from the SAR patients during allergy season but not in any sample before allergy season:  this protein was identified as eosinophil lysophospholipase (Charcot-Leyden crystal protein/galactin 10). MS/MS analysis of the N-terminus of the protein showed removal of Met and acetylation of Ser. Altogether, these findings illustrate the potential use of proteomics for identifying protein changes associated with allergic rhinitis and for revealing post-translational modifications of such new potential markers of allergic inflammation.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-32843 (URN)10.1021/pr050341h (DOI)18783 (Local ID)18783 (Archive number)18783 (OAI)
    Available from: 2009-10-09 Created: 2009-10-09 Last updated: 2017-12-13Bibliographically approved
  • 22.
    Ghafouri, Bijar
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
    Anderson, Chris
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Dermatology and Venerology.
    Microdialysis in Profiling Cytokines and Other Macromolecules in the Skin in Health and Disease: A Comment to Falcone et al.2017In: Acta Dermato-Venereologica, ISSN 0001-5555, E-ISSN 1651-2057, Vol. 97, no 10, p. 1269-1269Article in journal (Other academic)
    Abstract [en]

    n/a

  • 23.
    Ghafouri, Bijar
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center. PAINOMICS Lab, Linkoping, Sweden.
    Bäckryd, Emmanuel
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
    Proteomics in chronic pain; investigating mechanistic markers of pain2019In: Journal of Proteomics, ISSN 1874-3919, E-ISSN 1876-7737, Vol. 190, p. III-IIIArticle in journal (Other academic)
    Abstract [en]

    n/a

  • 24.
    Ghafouri, Bijar
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
    Carlsson, Anders
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
    Holmberg, Sara
    Department Research and Dev, Sweden.
    Thelin, Anders
    Uppsala University, Sweden.
    Tagesson, Christer
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Occupational and Environmental Medicine Center.
    Biomarkers of lsystemic inflammation in farmers with musculoskeletal disorders; a plasma proteomic study2016In: BMC Musculoskeletal Disorders, ISSN 1471-2474, E-ISSN 1471-2474, Vol. 17, no 206Article in journal (Refereed)
    Abstract [en]

    Background: Farmers have an increased risk for musculoskeletal disorders (MSD) such as osteoarthritis of the hip, low back pain, and neck and upper limb complaints. The underlying mechanisms are not fully understood. Workrelated exposures and inflammatory responses might be involved. Our objective was to identify plasma proteins that differentiated farmers with MSD from rural referents. Methods: Plasma samples from 13 farmers with MSD and rural referents were included in the investigation. Gel based proteomics was used for protein analysis and proteins that differed significantly between the groups were identified by mass spectrometry. Results: In total, 15 proteins differed significantly between the groups. The levels of leucine-rich alpha-2-glycoprotein, haptoglobin, complement factor B, serotransferrin, one isoform of kininogen, one isoform of alpha-1-antitrypsin, and two isoforms of hemopexin were higher in farmers with MSD than in referents. On the other hand, the levels of alpha-2-HS-glycoprotein, alpha-1B-glycoprotein, vitamin D-binding protein, apolipoprotein A1, antithrombin, one isoform of kininogen, and one isoform of alpha-1-antitrypsin were lower in farmers than in referents. Many of the identified proteins are known to be involved in inflammation. Conclusions: Farmers with MSD had altered plasma levels of protein biomarkers compared to the referents, indicating that farmers with MSD may be subject to a more systemic inflammation. It is possible that the identified differences of proteins may give clues to the biochemical changes occurring during the development and progression of MSD in farmers, and that one or several of these protein biomarkers might eventually be used to identify and prevent work-related MSD.

  • 25.
    Ghafouri, Bijar
    et al.
    Linköping University, Department of Molecular and Clinical Medicine, Occupational and Environmental Medicine. Linköping University, Faculty of Health Sciences.
    Irander, Kristina
    Linköping University, Department of Neuroscience and Locomotion, Oto-Rhiono-Laryngology and Head & Neck Surgery. Linköping University, Faculty of Health Sciences.
    Lindbom, John
    Linköping University, Department of Molecular and Clinical Medicine, Occupational and Environmental Medicine. Linköping University, Faculty of Health Sciences.
    Tagesson, Christer
    Linköping University, Department of Molecular and Clinical Medicine, Occupational and Environmental Medicine. Linköping University, Faculty of Health Sciences.
    Lindahl, Mats
    Linköping University, Department of Molecular and Clinical Medicine, Occupational and Environmental Medicine. Linköping University, Faculty of Health Sciences.
    Comparative proteomics of nasal fluid in seasonal allergic rhinitis2006In: Journal of Proteome Research, ISSN 1535-3893, E-ISSN 1535-3907, Vol. 5, no 2, p. 330-338Article in journal (Refereed)
    Abstract [en]

    A comparative proteomic approach was applied to examine nasal lavage fluid (NLF) from patients with seasonal allergic rhinitis (SAR, n = 6) and healthy subjects (controls, n = 5). NLF samples were taken both before allergy (pollen) season and during season, and proteins were analyzed by two-dimensional gel electrophoresis (2-DE) and matrix assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) after tryptic cleavage. Twenty proteins were selected and quantified. During allergy season, the levels of six sialylated isoforms of PLUNC (palate lung nasal epithelial clone) were lower in SAR patients than controls, as were the levels of six isoforms of von Ebner's gland protein (VEGP), including a previously undescribed form with N-linked glycosylation, and of cystatin S. PLUNC is a new innate immunity protein and VEGP and cystatin S are two endogenous proteinase inhibitors. By contrast, the levels of an acidic form of alpha-1-antitrypsin were higher in SAR patients than controls. One previously unidentified NLF protein was found in all samples from the SAR patients during allergy season but not in any sample before allergy season:  this protein was identified as eosinophil lysophospholipase (Charcot-Leyden crystal protein/galactin 10). MS/MS analysis of the N-terminus of the protein showed removal of Met and acetylation of Ser. Altogether, these findings illustrate the potential use of proteomics for identifying protein changes associated with allergic rhinitis and for revealing post-translational modifications of such new potential markers of allergic inflammation.

  • 26.
    Ghafouri, Bijar
    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. Linköping University, Faculty of Health Sciences.
    Lewander, Andreas
    Linköping University, Department of Clinical and Experimental Medicine, Oncology . 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.
    Lindahl, Mats
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Peptide mass fingerprint data from silver stained proteins can be improved by using 2,5-dihydroxybenzoic acid instead of α-cyano-4-hydroxycinnamic acid as matrix in MALDI-TOF MS2007Article in journal (Refereed)
  • 27.
    Ghafouri, Bijar
    et al.
    Linköping University, Department of Molecular and Clinical Medicine, Occupational and Environmental Medicine. Linköping University, Faculty of Health Sciences.
    Karlsson, Helen
    Linköping University, Department of Molecular and Clinical Medicine, Occupational and Environmental Medicine. Linköping University, Faculty of Health Sciences.
    Mörtstedt, Harriet
    Linköping University, Department of Molecular and Clinical Medicine. Linköping University, Faculty of Health Sciences.
    Lewander, Andreas
    Linköping University, Department of Biomedicine and Surgery. Linköping University, Faculty of Health Sciences.
    Tagesson, Christer
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Occupational and Environmental Medicine. Östergötlands Läns Landsting, Pain and Occupational Centre, Occupational and Environmental Medicine Centre.
    Lindahl, Mats
    Linköping University, Department of Molecular and Clinical Medicine, Occupational and Environmental Medicine. Linköping University, Faculty of Health Sciences.
    Note: 2,5-Dihydroxybenzoic acid instead of α-cyano-4-hydroxycinnamic acid as matrix in matrix-assisted laser desorption/ionization time-of-flight mass spectrometry for analyses of in-gel digests of silver-stained proteins: in Analytical Biochemistry(ISSN 0003-2697), vol 371, issue 1, pp 121-1232007In: Analytical Biochemistry, ISSN 0003-2697, E-ISSN 1096-0309, Vol. 371, no 1, p. 121-123Article in journal (Other academic)
    Abstract [en]

    [No abstract available]

  • 28.
    Ghafouri, Bijar
    et al.
    Linköping University, Department of Molecular and Clinical Medicine, Occupational and Environmental Medicine. Linköping University, Faculty of Health Sciences.
    Kihlström, Erik
    Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Microbiology. Linköping University, Faculty of Health Sciences.
    Ståhlbom, Bengt
    Linköping University, Department of Molecular and Clinical Medicine, Occupational and Environmental Medicine. Linköping University, Faculty of Health Sciences.
    Tagesson, Christer
    Linköping University, Department of Molecular and Clinical Medicine, Occupational and Environmental Medicine. Linköping University, Faculty of Health Sciences.
    Lindahl, Mats
    Linköping University, Department of Molecular and Clinical Medicine, Occupational and Environmental Medicine. Linköping University, Faculty of Health Sciences.
    PLUNC (palate, lung and nasal epithelial clone) proteins in human nasal lavage fluid2003In: Biochemical Society Transactions, ISSN 0300-5127, E-ISSN 1470-8752, Vol. 31, no 4, p. 810-814Article in journal (Refereed)
    Abstract [en]

    PLUNC (palate, lung and nasal epithelial clone) is a newly discovered gene that is expressed in the upper respiratory tract and is suggested to be of importance in host defence against bacteria. We have identified two forms of the PLUNC protein in human nasal lavage fluid (NLF) using two-dimensional gel electrophoresis (2-DE) and MS. The apparent molecular masses and isoelectric points of these forms are 24.8 kDa/pI 5.4 and 25.1 kDa/pI 5.5. Notably, the 24.8 kDa/pI 5.4 form of PLUNC is an abundant protein in the 2-DE protein patterns of NLF from healthy subjects. Decreased levels of PLUNC were found in NLF from smokers and workers exposed to reactive epoxy chemicals, indicating that long-term exposure to airway irritants impairs the production of PLUNC in the upper respiratory tract. We have also investigated the presence of lipopolysaccharide (LPS)-binding proteins in NLF. Five proteins were found to adsorb to a LPS-coated surface; two of these proteins correspond to the two PLUNC forms, as judged by 2-DE pattern matching. For comparison, human saliva was found to contain a set of LPS-binding proteins with similar 2-DE spot positions (the same pIs but somewhat lower apparent molecular masses of 20 kDa). These results indicate that PLUNC may be a new marker of airway inflammation and may play a part in the innate immune response, and that human saliva contains yet other members of the family of LPS-binding proteins.

  • 29.
    Ghafouri, Bijar
    et al.
    Linköping University, Department of Molecular and Clinical Medicine, Occupational and Environmental Medicine. Linköping University, Faculty of Health Sciences.
    Kihlström, Erik
    Linköping University, Department of Molecular and Clinical Medicine, Clinical Microbiology. Linköping University, Faculty of Health Sciences.
    Tagesson, Christer
    Linköping University, Department of Molecular and Clinical Medicine, Occupational and Environmental Medicine. Linköping University, Faculty of Health Sciences.
    Lindahl, Mats
    Linköping University, Department of Molecular and Clinical Medicine, Occupational and Environmental Medicine. Linköping University, Faculty of Health Sciences.
    PLUNC in human nasal lavage fluid: multiple isoforms that bind to lipopolysaccharide2004In: Biochimica et Biophysica Acta - Proteins and Proteomics, ISSN 1570-9639, E-ISSN 1878-1454, Vol. 1699, no 1-2, p. 57-63Article in journal (Refereed)
    Abstract [en]

    Here, we demonstrate the presence of multiple isoforms of palate lung nasal epithelial clone (PLUNC) in human nasal lavage fluid (NLF). Eight isoforms were separated by two-dimensional gel electrophoresis (2-DE), and peptide mapping of the proteins was performed using MALDI-TOF MS (matrix assisted laser desorption/ionization time of flight mass spectrometry) of tryptic and asparginase cleavages. The identification was verified by amino acid sequencing after analysis of collision-induced dissociation (CID) fragmentation spectra with nanoelectrospray MS/MS. One isoform showed an electrophoretic mobility shift after N-glycosidase treatment, indicating that at least one of the PLUNC isoforms is glycosylated. We also demonstrate that PLUNC in NLF binds to lipopolysaccharide (LPS) in vitro; indeed, out of all proteins present in NLF only the PLUNC isoforms were found to adsorb to an LPS-coated surface. These results show that PLUNC is expressed as multiple LPS-binding isoforms in human NLF. The possibility that PLUNC may play a role in the innate immune response of the upper airways is inferred.

  • 30.
    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.

  • 31.
    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.

  • 32.
    Ghafouri, Bijar
    et al.
    Linköping University, Department of Molecular and Clinical Medicine, Occupational and Environmental Medicine. Linköping University, Faculty of Health Sciences.
    Ståhlbom, Bengt
    Linköping University, Department of Molecular and Clinical Medicine, Occupational and Environmental Medicine. Linköping University, Faculty of Health Sciences.
    Tagesson, Christer
    Linköping University, Department of Molecular and Clinical Medicine, Occupational and Environmental Medicine. Linköping University, Faculty of Health Sciences.
    Lindahl, Mats
    Linköping University, Department of Molecular and Clinical Medicine, Occupational and Environmental Medicine. Linköping University, Faculty of Health Sciences.
    Newly identified proteins in human nasal lavage fluid from non-smokers and smokers using two-dimensional gel electrophoresis and peptide mass fingerprinting2002In: Proteomics, ISSN 1615-9853, E-ISSN 1615-9861, Vol. 2, no 1, p. 112-120Article in journal (Refereed)
    Abstract [en]

    Human nasal lavage fluids (NLFs) were analyzed with two-dimensional gel electrophoresis (2-DE) and proteins were identified with peptide mass fingerprinting using matrix-assisted laser desoption/ionization time of flight mass spectrometry. In some cases, the identification was verified by analysis of post-source decay fragmentation spectra. Many of the identified proteins were new forms or fragments of previously found proteins (e.g. albumin, lactoferrin, cystatin, calgranulin, von Ebners gland protein and palate lung nasal epithelium clone), while others were proteins that have previously been indicated by 2-DE image matching or immunoblots (e.g. apolipoprotein AI, lysozyme C, and Clara cell secretory protein). Some new proteins, not shown before in 2-DE patterns of NLF were also found, e.g. mammaglobin B, 2-microglobulin and immunoglobulin J chain. Of the identified NLF proteins many appear to be involved in inflammatory and immune responses. A study was therefore conducted to investigate if the levels of these proteins were changed in smokers compared to nonsmokers. It was found that NLF from smokers contained decreased levels of Clara cell secretory protein, and increased proportions of a truncated variant of lipocortin-1, three acidic forms of α1-antitrypsin, and one phosphorylated form of cystatin S. Furthermore, NLF from smokers contained increased proportions of a new variant of palate lung nasal epithelium clone (PLUNC), a recently identified airway irritation marker. The results demonstrate that 2-DE of NLF may be used to assess alterations of proteins or post-translationally modified proteins in smokers. Clara cell secretory protein (CC 16, CC 10) and lipocortin-1 are two anti-inflammatory, phospholipase A2 inhibitory proteins, and α1-antitrypsin and cystatin S are two proteinase inhibitors. Changed levels of these proteins may therefore be of importance to the airway inflammation caused by smoking. The results also support the notion that PLUNC is involved in inflammatory responses in the upper airways.

  • 33.
    Ghafouri, Bijar
    et al.
    Linköping University, Department of Molecular and Clinical Medicine, Occupational and Environmental Medicine. Linköping University, Faculty of Health Sciences.
    Tagesson, Christer
    Linköping University, Department of Molecular and Clinical Medicine, Occupational and Environmental Medicine. Linköping University, Faculty of Health Sciences.
    Lindahl, Mats
    Linköping University, Department of Molecular and Clinical Medicine, Occupational and Environmental Medicine. Linköping University, Faculty of Health Sciences.
    Mapping of proteins in human saliva using two-dimensional gel electrophoresis and peptide mass fingerprinting2003In: Proteomics, ISSN 1615-9853, E-ISSN 1615-9861, Vol. 3, no 6, p. 1003-1015Article in journal (Refereed)
    Abstract [en]

    Human saliva contains a large number of proteins that can be used for diagnosis and are of great potential in clinical and epidemiological research. The aim of this work was to map the proteins in saliva by two-dimensional gel electrophoresis (2-DE), and to identify abundant proteins by peptide mass fingerprinting using trypsin cleavage and matrix-assisted laser desorption/ionization-time of flight-mass spectrometry analysis. One hundred proteins were identified representing 20 different identities according to accession numbers. Abundant proteins expressed in different forms were: α-amylase, immunoglobulin A, prolactin-inducible protein, zinc-α2-glycoprotein and cystatins (S, SA, D and SN). Other proteins found were interleukin-1 receptor antagonist, von Ebner’s gland protein (lipocalin-1) and calgranulin A and B (S100A8 and A9). Furthermore, apolipoprotein A-I, β2-microglobulin, glutathione S-transferase P and fatty acid-binding protein were also identified. Our results show that human saliva contains a large number of proteins that are involved in inflammatory and immune responses. The 2-DE protein map constructed opens the possibility to investigate protein changes associated with disease processes.

  • 34.
    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.

  • 35.
    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.

  • 36.
    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.

  • 37.
    Grimby-Ekman, Anna
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Health Metrics, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Sweden Occupational and Environmental Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Sweden .
    Ghafouri, Bijar
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
    Sandén, H
    Occupational and Environmental Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Sweden..
    Larsson, Britt
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, 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 Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
    Different DHEA-S Levels and Response Patterns in Individuals with Chronic Neck Pain, Compared with a Pain Free Group-a Pilot Study.2017In: Pain medicine (Malden, Mass.), ISSN 1526-2375, E-ISSN 1526-4637, Vol. 18, no 5, p. 846-855Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To test, in this pilot study, whether DHEA-S (Dehydroepiandrosterone, sulfated form) plasma levels are lower among persons with chronic neck pain, compared to control persons, and to investigate the DHEA-S response after a physical exercise.

    SUBJECTS: Included were 12 persons with chronic neck pain and eight controls without present pain, all 18 and 65 years of age. Exclusion criteria for both groups were articular diseases or tendinosis, fibromyalgia, systemic inflammatory and neuromuscular diseases, pain conditions due to trauma, or severe psychiatric diseases.

    DESIGN AND METHODS: The participants arm-cycled on an ergometer for 30 minutes. Blood samples were taken before, 60 minutes, and 150 minutes after this standardized physical exercise.

    RESULTS: The estimated plasma DHEA-S levels at baseline were 2.0 µmol/L (95% confidence interval [CI] 1.00; 4.01) in the pain group and 4.1 µmol/L (95% CI2.0; 8.6) in the control group, adjusted for sex, age, body mass index (BMI), and Shirom-Melamed Burnout Questionnaire (SMBQ), with a ratio of 0.48 (P = 0.094).The total DHEA-S (AUCG) in the pain group were 183 min*µmol/L lower than in the control group (P = 0.068). For the response to the exercise (AUCI), the difference between the pain group and the control group was 148 min*µmol/L (P = 0.011).

    CONCLUSIONS: In this pilot study, the plasma DHEA-S levels appeared to be lower among the persons with chronic neck pain, compared with the control group. It was indicated that DHEA-S decreased during the physical exercise in the control group, and either increased or was unaffected in the chronic pain group.

  • 38.
    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.

  • 39.
    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.

  • 40.
    Hadrévi, Jenny
    et al.
    Umeå University, Sweden.
    Turkina, Maria
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Carlsson, Anders
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center. Linköping University, Faculty of Medicine and Health Sciences.
    Gerdle, Björn
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and 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 Medicine and Health Sciences. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
    Hellström, Fredrik
    University of Gävle, Sweden.
    Ghafouri, Bijar
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
    Myosin light chain and calcium regulating protein differences in chronic musculoskeletal neck and shoulder pain2016In: Journal of Integrated OMICS, ISSN 2182-0287, Vol. 6, no 1, p. 1-8Article in journal (Refereed)
    Abstract [en]

    Proteomic screening analysis has detected myosin light chain (MLC) as a protein implied to be involved in chronic musculoskeletal neck and shoulder pain. Several analyses of MLC proteins have stated a difference in phosphorylation being the determining factor for protein activation hence altered contrability of the muscle in i.e. senescence. In continuation of a previous publication, this study is an attempt to analyze the different MLC isoforms by mass spectrometry and immune-analyses in myalgic and healthy trapezius muscle. In the present study no differences in phosphorylation level between the corresponding individual proteins were detected using LC-MSMS and immunoblotting; instead we assigned different isoforms of regulatory MLCs. To further elucidate the contrability: calcium (Ca2+) regulatory proteins, sarco(endo)plasmic reticulum Ca2+ ATPase 1 (SERCA-1) and calsequestrine (CSQ) were analyzed by western blot. The analysis revealed a significantly increased abundance of SERCA-1 protein in the myalgic muscle and a significantly increased abundance of CSQ in healthy muscle. Myalgic muscle contraction patterns have in previous studies shown to differ from healthy muscle which may be connected to the Ca2+ availability in the muscle. Here we present the proteomic characterization of differences in Ca2+ regulating proteins and particularly regulatory MLCs in trapezius muscle of women with chronic musculoskeletal neck and shoulder pain.

  • 41.
    Håkansson, Irene
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Neurology.
    Gouveia-Figueira, Sandra
    Umea Univ, Sweden.
    Ernerudh, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    Vrethem, Magnus
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Neurology.
    Ghafouri, Nazdar
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, 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 Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
    Nording, Malin
    Umea Univ, Sweden; Univ Calif Davis, CA 95616 USA.
    Oxylipins in cerebrospinal fluid in clinically isolated syndrome and relapsing remitting multiple sclerosis2018In: Prostaglandins & other lipid mediators, ISSN 1098-8823, E-ISSN 2212-196X, Vol. 138, p. 41-47Article in journal (Refereed)
    Abstract [en]

    Although oxylipins are involved in inflammation, data on these lipid mediators in multiple sclerosis are sparse. In this study, a panel of oxylipins were analysed swith liquid chromatography tandem mass spectrometry in cerebrospinal fluid (CSF) from 41 treatment naive patients with clinically isolated syndrome (CIS) or relapsing remitting MS (RRMS) and 22 healthy controls. CSF levels of 9-hydroxyoctadecadienoic acid (9-HODE) and 13-hydroxyoctadecadienoic acid (13-HODE) were significantly higher in patients than in healthy controls (9-HODE median 380 nM (interquartile range 330-450 nM) in patients and 290 nM (interquartile range 250-340 nM) in controls, 13-HODE median 930 nM (interquartile range 810-1080 nM) in patients and 690 nM (interquartile range 570-760 nM) in controls, p amp;lt; 0.001 in Mann-Whitney U tests). 9-HODE and 13-HODE performed well for separation of patients and healthy controls (AUC 0.85 and 0.88, respectively, in ROC curve analysis). However, baseline CSF levels of the oxylipins did not differ between patients with signs of disease activity during one, two and four years of follow-up and patients without. In conclusion, this study indicates that 9-HODE and 13-HODE levels are increased in CSF from CIS and RRMS patients compared with healthy controls, but does not support 9-HODE or 13-HODE as prognostic biomarkers of disease activity in patients during follow-up.

  • 42.
    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.

  • 43.
    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.

  • 44.
    Jablochkova, Anna
    et al.
    Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
    Bäckryd, Emmanuel
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
    Kosek, Eva
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden; Karolinska Univ Hosp, Sweden.
    Mannerkorpi, Kaisa
    Univ Gothenburg, Sweden.
    Ernberg, Malin
    Karolinska Inst, Sweden; SCON, Sweden.
    Gerdle, Björn
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, 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 Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
    UNALTERED LOW NERVE GROWTH FACTOR AND HIGH BRAIN-DERIVED NEUROTROPHIC FACTOR LEVELS IN PLASMA FROM PATIENTS WITH FIBROMYALGIA AFTER A 15-WEEK PROGRESSIVE RESISTANCE EXERCISE2019In: Journal of Rehabilitation Medicine, ISSN 1650-1977, E-ISSN 1651-2081, Vol. 51, no 10, p. 779-787Article in journal (Refereed)
    Abstract [en]

    Background: The pathophysiology of fibromyalgia includes central and peripheral factors. Neurotro-phins, such as nerve growth factor and brain-derived neurotrophic factor, are involved in peripheral and central nervous system development of pain and hyperalgesia. Few studies have examined circulating nerve growth factor and brain-derived neurotrophic factor in fibromyalgia or have investigated whether exercise interventions affect the levels of these peptides. Objectives: To compare plasma levels of nerve growth factor and brain-derived neurotrophic factor in fibromyalgia and in healthy controls, to investigate correlations between levels of nerve growth factor, brain-derived neurotrophic factor, and cytokines and clinical variables, and to investigate the effect of exercise on these levels. Subjects and methods: A total of 75 women with fibromyalgia participated in blood tests at baseline and after the 15-week intervention, and 25 healthy controls participated at baseline. Patients were randomized to a 15-week progressive resistance exercise intervention or a relaxation intervention. Results: Brain-derived neurotrophic factor level was significantly higher (p amp;lt;0.001) and nerve growth factor level was significantly lower (p amp;lt;0.001) in fibromyalgia than in healthy controls. Neither resistance exercise nor relaxation interventions affected the levels of brain-derived neurotrophic factor or nerve growth factor. No significant correlations were found between brain-derived neurotrophic factor or nerve growth factor plasma levels in fibromyalgia and cytokine levels or clinical variables. Conclusion: Changes in circulating nerve growth factor and brain-derived neurotrophic factor levels may affect nociception/pain in fibromyalgia. Clinical improvements were achieved following the exercise intervention, but the levels of brain-derived neurotrophic factor and nerve growth factor were not normalized.

  • 45.
    Jasim, Hajer
    et al.
    Karolinska Inst, Sweden; Karolinska Inst, Sweden; Folktandvarden Stockholm AB, Sweden.
    Carlsson, Anders
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
    Hedenberg-Magnusson, Britt
    Karolinska Inst, Sweden; Karolinska Inst, Sweden; Folktandvarden Stockholm AB, Sweden.
    Ghafouri, Bijar
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
    Ernberg, Malin
    Karolinska Inst, Sweden; Karolinska Inst, Sweden.
    Saliva as a medium to detect and measure biomarkers related to pain2018In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 8, article id 3220Article in journal (Refereed)
    Abstract [en]

    Saliva is often neglected as a body fluid of diagnostic or prognostic value, even though generally well accepted by the patients. This is due to lack of a standardized collection procedure. The aim of this study was to identify the ideal saliva collection technique and develop new sensitive methods to detect and analyse markers related to pain in healthy pain-free subjects. Plasma and five different saliva collection approached was evaluated during strictly controlled conditions. Levels of nerve growth factor (NGF), calcitonin gene-related peptide (CGRP) and brain derived neurotropic factor (BDNF) were determined using novel western blotting based technology. Glutamate and substance P (SP) was determined using commercial available methods. Several new isoforms were found for NGF, CGRP and BDNF in saliva. The isoform pattern showed significant variation in both expression and chemiluminescence levels between different collection methods. New sensitive methods to study pain related markers in saliva were developed in this study. Furthermore, we are first to demonstrate a correlation between the Glutamate concentration in stimulated whole saliva and blood. However, the fundamental conclusion drawn is the importance of consistency in the collection method.

  • 46.
    Jasim, Hajer
    et al.
    Karolinska Institute, Sweden; Scandinavian Centre Orofacial Neurosci SCON, Sweden; Folktandvarden Stockholm AB, Sweden.
    Olausson, Patrik
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
    Hedenberg-Magnusson, Britt
    Karolinska Institute, Sweden; Scandinavian Centre Orofacial Neurosci SCON, Sweden; Folktandvarden Stockholm AB, Sweden.
    Ernberg, Malin
    Karolinska Institute, Sweden; Scandinavian Centre Orofacial Neurosci SCON, Sweden.
    Ghafouri, Bijar
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
    The proteomic profile of whole and glandular saliva in healthy pain-free subjects2016In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 6, article id 39073Article in journal (Refereed)
    Abstract [en]

    Determination of the variability in the salivary proteome is a prerequisite for the development of saliva as a diagnostic and prognostic tool in particular physiological states. In this context, it is important that technical variability induced by sample collection and processing is kept at minimum to be able to reproducibly assess variability in states of health and disease. In the current study, the proteome profile in unstimulated and stimulated whole, parotid and sublingual saliva was investigated using two-dimensional gel electrophoresis. Saliva samples were structurally collected from ten examined and characterized healthy individuals during the exactly same conditions. The results demonstrated that different collection methods provide clear differences in the snapshot of the salivary proteome and also in the relative amount of specific proteins. The variable nature of the salivary proteome suggests that different approaches may have to be adopted when studying its composition or its possible role as an indicator for particular physiological states. The results emphasize the importance of consistency when collecting saliva samples for proteomic analysis.

  • 47.
    Kallman, Thomas F.
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center. Linköping University, Faculty of Medicine and Health Sciences.
    Ghafouri, Bijar
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
    Bäckryd, Emmanuel
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
    Salivary beta-endorphin and substance P are not biomarkers of neuropathic chronic pain propensity2018In: Heliyon, ISSN 2405-8440, Vol. 4, no 8, article id e00718Article in journal (Refereed)
    Abstract [en]

    Objective

    The pathophysiology of chronic pain is complex, with most of our knowledge being derived from preclinical studies. The search for biomarkers mirroring the pathophysiology of chronic pain is ongoing, and there is an increasing interest in saliva as a diagnostic tool. Given what is known about salivary substance Pand salivary gland innervation, we hypothesized that salivary substance P and/or beta-endorphin might reflect the basal activity of these neuropeptides in the central nervous system, thereby perhaps mirroring a general propensity to chronic pain. Based on this overall hypothesis, our aim was to compare salivary levels of these neuropeptides in chronic neuropathic pain patients with healthy controls. An additional aim was to relate salivary levels to plasma levels.

    Materials and methods

    We compared salivary concentrations of beta-endorphin and substance P in 14 chronic neuropathic pain patients with concentrations in 18 healthy controls using a Luminex technology kit. Salivary-to-plasma quotients were also calculated.

    Results

    We found no significant difference between the groups' salivary concentrations of substance P and beta-endorphin. No correlation was found between salivary and plasma concentrations of each neuropeptide, which we hypothesize might point to local production of beta-endorphin and/or substance P in the salivary glands. Given high substance P salivary-to-plasma quotients, such a local production seems more likely for substance P than for beta-endorphin.

    Conclusions

    Propensity to neuropathic chronic pain was not substantiated by our analysis of salivary levels of substance P and/or beta-endorphin. However, we report salivary-to-plasma quotients that give potentially important physiological insight about these neuropeptides.

  • 48.
    Karlsson, Helen
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Occupational and Environmental Medicine.
    Ghafouri, Bijar
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Occupational and Environmental Medicine.
    Leanderson, Per
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Occupational and Environmental Medicine. Östergötlands Läns Landsting, Pain and Occupational Centre, Occupational and Environmental Medicine Centre.
    Lindahl, Mats
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Occupational and Environmental Medicine.
    Tagesson, Christer
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Occupational and Environmental Medicine. Östergötlands Läns Landsting, Pain and Occupational Centre, Occupational and Environmental Medicine Centre.
    Kartläggning av proteiner i LDL och HDL med två-dimensionell gelelektrofores samt masspektrometri.2003In: Svenska Läkaresällskapets Handlingar,2003, 2003, p. 11-26Conference paper (Refereed)
  • 49.
    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.

  • 50.
    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.

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