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  • 1. Alstergren, P
    et al.
    Ernberg, M
    Kopp, S
    Lundeberg, T
    Theodorsson, Elvar
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Clinical Chemistry. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Chemistry.
    TMJ pain in relation to circulating neuropeptide Y, serotonin, and interleukin-1 beta in rheumatoid arthritis.1999In: Journal of Orofacial Pain, ISSN 1064-6655, E-ISSN 1945-3396, Vol. 13, p. 49-55Article in journal (Refereed)
  • 2. Alstergren, P
    et al.
    Kopp, S
    Theodorsson, Elvar
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Clinical Chemistry. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Chemistry.
    Synovial fluid sampling fromthe temporomandibular joint: sample quality criteria and levels of interleukin-1 beta and serotonin.1999In: Acta Odontologica Scandinavica, ISSN 0001-6357, E-ISSN 1502-3850, Vol. 57, p. 16-22Article in journal (Refereed)
  • 3.
    Amatya, B
    et al.
    Karolinska University Hospital.
    El-Nour, H
    Karolinska University Hospital.
    Holst, M
    Astrid Lindgren Childrens Hospital.
    Theodorsson, Elvar
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Diagnostics, Department of Clinical Chemistry.
    Nordlind, K
    Karolinska University Hospital.
    Expression of tachykinins and their receptors in plaque psoriasis with pruritus2011In: BRITISH JOURNAL OF DERMATOLOGY, ISSN 0007-0963, Vol. 164, no 5, p. 1023-1029Article in journal (Refereed)
    Abstract [en]

    Pandgt;Background Cutaneous melanoma is rapidly increasing in incidence worldwide and approximately 5% of melanomas are hereditary. Deletions in chromosome 1p36 have been detected in melanoma but no candidate melanoma tumour suppressor gene has yet been found in this area. Recently, strong evidence has been reported that CHD5 is a tumour suppressor gene in this region. Objectives To investigate CHD5 involvement in familial melanoma. Methods Peripheral blood DNA from 47 melanoma families who do not carry mutations in any of the three currently recognized melanoma genes, 398 patients with sporadic melanoma and 398 geographically matched nonmelanoma-bearing controls were studied. Linkage investigation, single nucleotide polymorphism (SNP) genotyping and mutation screening studies were carried out on the CHD5 locus. Results The CHD5 gene was not excluded by linkage analysis in any of the families. On SNP genotyping, the CHD5 rs7513548 SNP was found to be significantly associated with sporadic melanoma (odds ratio 1 center dot 53, 95% confidence interval 1 center dot 13-2 center dot 06). The AG genotype was found in 208 cases and 169 controls (cf. 141 and 175 cases and controls, respectively, for the AA genotype). On CHD5 mutation screening, a total of 50 single-base substitutions were detected. Of these, 39 were intronic and 11 were exonic. While 32 were previously recognized variants, 18 were newly identified. Three, in exons 4, 31 and 32, led to nonsynonymous substitutions. A p.Met1576Ile substitution was identified in a mother and daughter, both with invasive cutaneous melanoma. Conclusions This study appears to be the first report of CHD5 variants in familial cutaneous melanoma. Such CHD5 variants could block or alter the ability of CHD5 to regulate the cell cycle pathway and to effect cellular control. As only one of the 47 families studied has this variant, it appears to be a rare event and further screening of melanoma families is required to confirm whether or not CHD5 is involved in melanoma pathogenesis.

  • 4. Andreen Sachs, Magna
    et al.
    Theodorsson, Elvar
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Clinical Chemistry. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Chemistry.
    Övergripande kvalitetsindikatorer framtagna för hälso- och sjukvården2002In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 99, p. 797-803Article in journal (Other academic)
  • 5.
    Andreen-Sachs, Magna
    et al.
    Hälso- och sjukvårdsnämndens stab, Stockholms läns landsting.
    Theodorsson, Elvar
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of clinical chemistry. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Chemistry.
    Overgripande kvalitetsindikatorer framtagna for halso- och sjukvarden2002In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 99, p. 797-803Article in journal (Other academic)
  • 6.
    Appelgren, A
    et al.
    St Eriks Hosp, Orofacial Pain & TMD Ctr, Stockholm, Sweden Karolinska Inst, S-10401 Stockholm, Sweden Linkoping Univ Hosp, S-58185 Linkoping, Sweden.
    Appelgren, BH
    St Eriks Hosp, Orofacial Pain & TMD Ctr, Stockholm, Sweden Karolinska Inst, S-10401 Stockholm, Sweden Linkoping Univ Hosp, S-58185 Linkoping, Sweden.
    Carleson, J
    Theodorsson, Elvar
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry. Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry.
    Lundberg, T
    St Eriks Hosp, Orofacial Pain & TMD Ctr, Stockholm, Sweden Karolinska Inst, S-10401 Stockholm, Sweden Linkoping Univ Hosp, S-58185 Linkoping, Sweden.
    Central and peripheral changes in neuropeptide Y-like immunoreactivity following adjuvant monoarthritis in the rat temporomandibular joint.2002In: Journal of Dental Research, ISSN 0022-0345, E-ISSN 1544-0591, Vol. 81, p. 3190-Conference paper (Other academic)
  • 7. Arnelo, Urban
    et al.
    Herrington, Margery
    Theodorsson, Elvar
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Clinical Chemistry. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Chemistry.
    Adrian, Thomas
    Reidelberger, Roger
    Larsson, Jörgen
    Marcusson, Jan
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Geriatrics. Östergötlands Läns Landsting, MC - Medicincentrum, Geriatrik-LAH.
    Strömmer, Lisa
    Ding, Xianzhong
    Permert, Johan
    Effects of long-term infusion of anorexic concentrations of islet amyloid polypeptide on neurotransmitters and neuropeptides in rat brain.2000In: Brain Research, ISSN 0006-8993, E-ISSN 1872-6240, Vol. 887, p. 391-398Article in journal (Refereed)
  • 8.
    Barklin, A.
    et al.
    Aarhus University Hospital.
    Theodorsson, Elvar
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Chemistry.
    Larsson, A.
    Aarhus University Hospital.
    Tyvold, S.
    Norwegian University of Science & Technology.
    Granfeldt, A.
    Aarhus University Hospital.
    Tonnesen, E.
    Aarhus University Hospital.
    Neuropeptides in brain death-induced neurogenic pulmonary edema2009In: in ACTA ANAESTHESIOLOGICA SCANDINAVICA, vol 53, 2009, Vol. 53, p. 45-45Conference paper (Refereed)
    Abstract [en]

    n/a

  • 9.
    Barklin, Anne
    et al.
    Aarhus University Hospital.
    Theodorsson, Elvar
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Chemistry.
    Tyvold, Stig S
    Norwegian Univ Science & Technology.
    Larsson, Anders
    Aarhus University Hospital.
    Granfeldt, Asger
    Aarhus University Hospital.
    Sloth, Erik
    Aarhus University Hospital.
    Tonnesen, Else
    Aarhus University Hospital.
    Alteration of Neuropeptides in the Lung Tissue Correlates Brain Death-Induced Neurogenic Edema2009In: JOURNAL OF HEART AND LUNG TRANSPLANTATION, ISSN 1053-2498, Vol. 28, no 7, p. 725-732Article in journal (Refereed)
    Abstract [en]

    Background: increased intracranial pressure induces neurogenic pulmonary edema (NPE), potentially explaining why only lungs from less than 20% of brain dead organ donors can be used for transplantation. This study investigated the underlying mechanisms of NPE, focusing on neuropeptides, which potently induce vasoconstriction, vasodilatation, and neurogenic inflammation. Methods: Brain death was induced in 10 pigs by increasing the intracranial pressure. Eight additional pigs served as controls. Neuropeptide Y (NPY), calcitonin gene-related peptide (CGRP), and substance P were analyzed in plasma, bronchoalveolar lavage (BAL) fluid, and homogenized lung tissue 6 hours after brain death. Pulmonary oxygen exchange was estimated using partial pressure of arterial oxygen (Pao(2))/fraction of inspired oxygen (FIO2), and pulmonary edema by wet/dry weight ratio. Results: Brain death induced a decrease in PaO2/FIO2 (P less than 0.001) and increased the wet/dry weight of both apical (p = 0.01) and basal lobes (p = 0.03). NPY and CGRP concentrations were higher in the BAL fluid of brain-dead animals compared with controls (p = 0.02 and p = 0.02) and were positively correlated with the wet/dry weight ratio. NPY content in lung tissue was lower in brain-dead animals compared with controls (p = 0.04) and was negatively correlated with the wet/dry weight ratio. There were no differences in substance P concentrations between the groups. Conclusion: NPY was released from the lung tissue of brain-dead pigs, and its concentration was related to the extent of pulmonary edema. NPY may be one of several crucial mediators of neurogenic pulmonary edema, raising the possibility of treatment with NPY-antagonists to increase the number of available lung donors.

  • 10.
    Bergdahl, Björn
    et al.
    Linköping University, Faculty of Health Sciences.
    Eintrei, Christina
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medical and Health Sciences.
    Fyrenius, Anna
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medical and Health Sciences.
    Hultman, Per
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine.
    Ledin, Torbjörn
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Division of Neuroscience.
    Theodorsson, Elvar
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine.
    In the Forefront of Development:The New Undergraduate Medical Curriculu2006In: Celebrating the Past by Expanding the Future: The Faculty of Health Science, Linköping University 1986–2006 / [ed] Mats Hammar, Björn Bergdahl, Lena Öhman, Linköping: Linköping University Electronic Press, 2006, 1, p. 98-102Chapter in book (Other academic)
  • 11.
    Bergdahl, Björn
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care. Östergötlands Läns Landsting, Heart Centre, Department of Cardiology.
    Eintrei, Christina
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Anaesthesiology. Östergötlands Läns Landsting, Anaesthesiology and Surgical Centre, Department of Intensive Care UHL.
    Fyrenius, Anna
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Clinical Physiology.
    Hultman, Per
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Molecular and Immunological Pathology. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Pathology and Clinical Genetics.
    Theodorsson, Elvar
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of clinical chemistry. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Chemistry.
    Läkarutbildningen i Linköpings förnyas. Problembaserat lärande, basvetenskap och folkhälsa förstärks2005In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 102, no 38, p. 2654-2658Article in journal (Other academic)
  • 12. Bjellerup, P
    et al.
    Theodorsson, Elvar
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Clinical Chemistry. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Chemistry.
    Jörnvall, H
    Kogner, P
    Limited neuropeptide Y precursor processing in unfavourable metastatic neuroblastoma tumours2000In: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 83, no 2, p. 171-176Article in journal (Refereed)
    Abstract [en]

    Neuropeptide Y (NPY) is found at high concentrations in neural crest-derived tumours and has been implicated as a regulatory peptide in tumour growth and differentiation. Neuroblastomas, ganglioneuromas and phaeochromocytomas with significant concentrations of NPY-like immunoreactivity were investigated for different molecular forms of NPY and for significance of proNPY processing. Gel-permeation chromatography identified intact NPY (1-36) in all tumours, whereas proNPY (69 amino acids) was detected only in control adrenal tissue and malignant neuroblastomas. Purification of NPY-like immunoreactivity in tumour extracts and structural characterization revealed that both NPY (1-36) and the truncated form NPY (3-36) was present. The degree of processing of proNPY to NPY in tumour tissue was lower in advanced neuroblastomas with regional or metastatic spread (stage 3 and 4) (n = 6), (41%, 12-100%, median, range), compared to the less aggressive stage 1, 2 and 4S tumours (n = 12), (93%, 69-100%), (P = 0.012). ProNPY processing of less than 50% was correlated with poor clinical outcome (P = 0.004). MYCN oncogene amplification was also correlated to a low degree of proNPY processing (P = 0.025). In summary, a low degree of proNPY processing was correlated to clinical advanced stage and poor outcome in neuroblastomas. ProNPY/NPY processing generated molecular forms of NPY with known differences in NPY-receptor selectivity, implicating a potential for in vivo modulation of NPY-like effects in tumour tissue. (C) 2000 Cancer Research Campaign.

  • 13.
    Bjerner, Johan
    et al.
    University of Oslo.
    Theodorsson, Elvar
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Chemistry.
    Hovig, Eivind
    Norwegian Radium Hospital.
    Kallner, Anders
    Karolinska University Hospital.
    Non-parametric estimation of reference intervals in small non-Gaussian sample sets2009In: ACCREDITATION AND QUALITY ASSURANCE, ISSN 0949-1775, Vol. 14, no 4, p. 185-192Article in journal (Refereed)
    Abstract [en]

    This study aimed at validating common bootstrap algorithms for reference interval calculation.We simulated 1500 random sets of 50-120 results originating from eight different statistical distributions. In total, 97.5 percentile reference limits were estimated from bootstrapping 5000 replicates, with confidence limits obtained by: (a) normal, (b) from standard error, (c) bootstrap percentile (as in RefVal) (d) BCa, (e) basic, or (f) student methods. Reference interval estimates obtained with ordinary bootstrapping and confidence intervals by percentile method were accurate for distributions close to normality and devoid of outliers, but not for log-normal distributions with outliers. Outlier removal and transformation to normality improved reference interval estimation, and the basic method was superior in such cases. In conclusions, if the neighborhood of the relevant percentile contains non-normally distributed results, bootstrapping fails. The distribution of bootstrap estimates should be plotted, and a non-normal distribution should warrant transformation or outlier removal.

  • 14.
    Boknäs, Niklas
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences.
    Faxälv, Lars
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Clinical Chemistry.
    Ström, Jakob O
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences.
    Tengvall, Pentti
    Sahlgrenska Academy, University of Gothenburg, Sweden.
    Theodorsson, Elvar
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Clinical Chemistry.
    Ramström, Sofia
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences.
    Lindahl, Tomas L
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Clinical Chemistry.
    Response: platelets do not generate activated factor XII--how inappropriate experimental models have led to misleading conclusions2014In: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 124, no 10, p. 1692-1694Article in journal (Other academic)
  • 15.
    Borud, Einar Kristian
    et al.
    University of Tromso.
    Alraek, Terje
    University of Tromso.
    White, Adrian
    University of Exeter.
    Fonnebo, Vinjar
    University of Tromso.
    Eggen, Anne Elise
    University of Tromso.
    Hammar, Mats
    Linköping University, Department of Clinical and Experimental Medicine, Obstetrics and gynecology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Gynecology and Obstetrics in Linköping.
    Lindh-Åstrand, Lotta
    Linköping University, Department of Clinical and Experimental Medicine, Obstetrics and gynecology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Gynecology and Obstetrics in Linköping.
    Theodorsson, Elvar
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Chemistry.
    Grimsgaard, Sameline
    University of Tromso.
    The Acupuncture on Hot Flushes Among Menopausal Women (ACUFLASH) study, a randomized controlled trial2009In: MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY, ISSN 1072-3714, Vol. 16, no 3, p. 484-493Article in journal (Refereed)
    Abstract [en]

    Objective: This study compared the effectiveness of individualized acupuncture plus self-care versus self-care alone on hot flashes and health-related quality of life in postmenopausal women.

    Methods: This study involved a multicenter, pragmatic, randomized, controlled trial with two parallel arms. Participants were postmenopausal women experiencing, on average, seven or more hot flashes per 24 hours during seven consecutive days. The acupuncture group received 10 acupuncture treatment sessions and advice on self-care, and the control group received advice on self-care only. The frequency and severity (0-10 scale) of hot flashes were registered in a diary. Urine excretion of calcitonin gene-related peptide was assessed at baseline and after 12 weeks. The primary endpoint was change in mean hot flash frequency from baseline to 12 weeks. The secondary endpoint was change in health-related quality of life measured by the Womens Health Questionnaire.

    Results: Hot flash frequency decreased by 5.8 per 24 hours in the acupuncture group (n = 134) and 3.7 per 24 hours in the control group (n = 133), a difference of 2.1 (P < 0.001). Hot flash intensity decreased by 3.2 units in the acupuncture group and 1.8 units in the control group, a difference of 1.4 (P < 0.001). The acupuncture group experienced statistically significant improvements in the vasomotor, sleep, and somatic symptoms dimensions of the Womens Health Questionnaire compared with the control group. Urine calcitonin gene-related peptide excretion remained unchanged from baseline to week 12.

    Conclusions: Acupuncture plus self-care can contribute to a clinically relevant reduction in hot flashes and increased health-related quality of life in postmenopausal women.

  • 16. Bracci-Laudiero, Luisa
    et al.
    Aloe, Luigi
    Buanne, Pasquale
    Finn, Anja
    Stenfors, Carina
    Vigneti, Eliana
    Theodorsson, Elvar
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Clinical Chemistry. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Chemistry.
    Lundeberg, Thomas
    NGF modulates CGRP synthesis in human B-lymphocytes: A possible anti-inflammatory action of NGF?2002In: Journal of Neuroimmunology, ISSN 0165-5728, E-ISSN 1872-8421, Vol. 123, no 1-2, p. 58-65Article in journal (Refereed)
    Abstract [en]

    We investigated whether the sensory neuropeptide, calcitonin gene-related peptide (CGRP), could be synthesised by human lymphocytes. Our results indicate that in activated B-cells, there is a strong expression of CGRP gene transcripts, which is almost absent in resting cells. Since B-cells autocrinally produce NGF, the neutralisation of endogenous NGF by anti-NGF antibodies resulted in a marked reduction in CGRP expression in both resting and activated B-cells. Thus, NGF appears to directly affect the synthesis of CGRP in B-cells as in sensory neurons. By regulating CGRP synthesis in lymphocytes and neuronal cells, NGF can influence the intensity and duration of the immune response. ⌐ 2002 Elsevier Science B.V. All rights reserved.

  • 17. Bracci-Laudiero, Luisa
    et al.
    Aloe, Luigi
    Lundeberg, Thomas
    Theodorsson, Elvar
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Clinical Chemistry. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Chemistry.
    Stenfors, Carina
    Altered levels of neuropeptides characterize the brain of lupus prone mice.1999In: Neuroscience Letters, ISSN 0304-3940, E-ISSN 1872-7972, Vol. 273Article in journal (Refereed)
  • 18.
    Brynhildsen, Jan
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Obstetrics and gynecology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping.
    Sydsjö, Gunilla
    Linköping University, Department of Clinical and Experimental Medicine, Obstetrics and gynecology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping.
    Blomberg, Marie
    Linköping University, Department of Clinical and Experimental Medicine, Obstetrics and gynecology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping.
    Claesson, Ing-Marie
    Linköping University, Department of Clinical and Experimental Medicine, Obstetrics and gynecology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping.
    Theodorsson, Elvar
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Clinical Chemistry.
    Nyström, Fredrik H.
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Endocrinology.
    Sydsjö, Adam
    Linköping University, Department of Clinical and Experimental Medicine, Obstetrics and gynecology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping.
    Josefsson, Ann
    Linköping University, Department of Clinical and Experimental Medicine, Obstetrics and gynecology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping.
    Leptin and adiponectin in cord blood from children of normal weight, overweight and obese mothers2013In: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227, Vol. 102, no 6, p. 620-624Article in journal (Refereed)
    Abstract [en]

    Aim To study cord blood concentrations of adiponectin and leptin in children born by normal weight, overweight and obese mothers and to study these parameters in relation to a weight gain intervention programme for obese mothers. Methods Ten millilitre cord blood was collected and analysed for leptin and adiponectin concentrations in children with gestational age andgt;37weeks born by 60 normal weight, 45 overweight and 145 obese mothers. 82 obese mothers took part in a weight gain intervention programme. Results Concentrations of leptin and adiponectin were higher in cord blood from children of overweight and obese mothers compared with children of normal weight mothers (leptin: Md 13.2, 30, 3 and 90.2ng/mL respectively, pandlt;0.001; adiponectin 35.9, 205.4, 213.8ng/L pandlt;0.001). No differences were found between overweight and obese mothers. The weight gain intervention programme for obese pregnant women had significant effects on the weight gain during pregnancy but had no effects on cord blood serum concentrations of leptin and adiponectin. Conclusion Cord blood leptin and adiponectin concentrations were higher in children born by overweight or obese women compared with children of normal weight mothers. A weight gain intervention programme for obese pregnant women did not affect these results. Intrauterine exposition to high concentrations of leptin and adiponectin may play a role in weight development later in life.

  • 19.
    Carlson, Joyce
    et al.
    Lunds universitet.
    Theodorsson, Elvar
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Clinical Chemistry.
    Lindstedt, Göran
    Sahlgrenska akademin, Göteborgs universitet.
    Digestionsorganens sjukdomar2012In: Laurells Klinisk kemi i praktisk medicin / [ed] Peter Nilsson-Ehle, Maria Berggren Söderlund, Elvar Theodorsson, Lund: Studentlitteratur, 2012, 9, p. 441-496Chapter in book (Other academic)
    Abstract [sv]

    Klinisk kemi i praktisk medicin används som kurslitteratur för läkare, biomedicinska analytiker och biomedicinare sedan 40 år tillbaka. Den finns på avdelningar, mottagningar och vårdcentraler - överallt där man behöver ta prover för kliniskt kemiska analyser och tolka deras resultat. Nu föreligger den i sin nionde upplaga efter omfattande revision och med nyskrivna kapitel. I denna upplaga har innehållet organiserats med tydlig anknytning till kliniska problemområden. Alla kapitel har grundligt reviderats. Avsnitten om tolkning av analysresultat, allergi och autoimmunitet, hjärtinfarkt och hjärtskademarkörer, digestionsorganens sjukdomar, graviditet, infertilitet och prenataldiagnostik samt läkemedel, förgiftningar och missbruk är helt nyskrivna. Boken kan användas både för att slå upp fakta om specifika analyser och för att förstå de sjukdomsmekanismer som är av betydelse för tolkningen av laboratorieresultat. Modern medicinsk praxis är patientcentrerad och har sitt fundament i ett nära samspel mellan klinik, laboratorier och patienter. Kunskapsfragment inom klinisk kemi är lättillgängliga för alla och envar på nätet, men ger sällan den helhetsbild som behövs för grundlig förståelse och därmed optimal användning av laboratorieanalyser. Denna bok ger sådan helhetsbild.

  • 20.
    Choremi-Papadopoulou, Helen
    et al.
    Immunologu Department Laiko General Hospital.
    Faure, Gilbert C.
    Laboratorie dImmunologie Université Henri Poincaré.
    Grunnet, Niels
    Department of Clinical Immunology Aarhus University Hospital.
    Madden, Michael
    Dept. Haematology Mercy University Hospital.
    Malenica, Branko
    Department of Immunology University Center Zagreb.
    Misbah, Siraj A
    Department of Clinical Immunology Oxford Radcliffe Hospitals.
    Theodorsson, Elvar
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of clinical chemistry. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Chemistry.
    Zlabinger, Gerhard J
    Institute of Immunology Medical University of Vienna.
    Position statement: Training programme in immunology of the European Board of UEMS Medical Biopathology [2]2005In: Immunology Letters, ISSN 0165-2478, E-ISSN 1879-0542, Vol. 96, no 2, p. 305-310Article in journal (Refereed)
  • 21. Dawidson, I
    et al.
    Angmar-Mansson, B
    Blom, M
    Theodorsson, Elvar
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Clinical Chemistry. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Chemistry.
    Lundeberg, T
    Sensory stimulation (acupuncture) increases the release of calcitonin gene-related peptide in the saliva os xerostomia sufferers.1999In: Neuropeptides, ISSN 0143-4179, E-ISSN 1532-2785, Vol. 33, p. 244-250Article in journal (Refereed)
  • 22.
    Dawidson, I
    et al.
    Karolinska Inst, Dept Cardiol, Stockholm, Sweden Karolinska Inst, Dept Physiol & Pharmacol, Stockholm, Sweden Linkoping Univ Hosp, Dept Clin Chem, S-58185 Linkoping, Sweden.
    Blom, M
    Karolinska Inst, Dept Cardiol, Stockholm, Sweden Karolinska Inst, Dept Physiol & Pharmacol, Stockholm, Sweden Linkoping Univ Hosp, Dept Clin Chem, S-58185 Linkoping, Sweden.
    Angmar-Mansson, B
    Karolinska Inst, Dept Cardiol, Stockholm, Sweden Karolinska Inst, Dept Physiol & Pharmacol, Stockholm, Sweden Linkoping Univ Hosp, Dept Clin Chem, S-58185 Linkoping, Sweden.
    Theodorsson, Elvar
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry. Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry.
    Lundeberg, T
    Karolinska Inst, Dept Cardiol, Stockholm, Sweden Karolinska Inst, Dept Physiol & Pharmacol, Stockholm, Sweden Linkoping Univ Hosp, Dept Clin Chem, S-58185 Linkoping, Sweden.
    Sensory stimulation (acupuncture) increases the release of CGRP and VIP in the saliva of xerostomic patients1999In: Brain Research, ISSN 0006-8993, E-ISSN 1872-6240, Vol. 848, no 1-2, p. P62-Conference paper (Other academic)
  • 23.
    Dawidson, I
    et al.
    Karolinska Inst, Dept Cariol, Stockholm, Sweden Linkoping Univ Hosp, Dept Clin Chem, S-58185 Linkoping, Sweden Karolinska Inst, Dept Physiol & Pharmacol, Stockholm, Sweden.
    Blom, M
    Karolinska Inst, Dept Cariol, Stockholm, Sweden Linkoping Univ Hosp, Dept Clin Chem, S-58185 Linkoping, Sweden Karolinska Inst, Dept Physiol & Pharmacol, Stockholm, Sweden.
    Angmar-Mansson, B
    Karolinska Inst, Dept Cariol, Stockholm, Sweden Linkoping Univ Hosp, Dept Clin Chem, S-58185 Linkoping, Sweden Karolinska Inst, Dept Physiol & Pharmacol, Stockholm, Sweden.
    Theodorsson, Elvar
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry. Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry.
    Lundeberg, T
    Karolinska Inst, Dept Cariol, Stockholm, Sweden Linkoping Univ Hosp, Dept Clin Chem, S-58185 Linkoping, Sweden Karolinska Inst, Dept Physiol & Pharmacol, Stockholm, Sweden.
    Sensory stimulation increases salivary CGRP and VIP in xerostomic patients.2001In: Journal of Dental Research, ISSN 0022-0345, E-ISSN 1544-0591, Vol. 80, no 4, p. 1302-1302Conference paper (Other academic)
  • 24.
    Dock, Hua
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Theodorsson, Annette
    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, Department of Neurosurgery.
    Theodorsson, Elvar
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Chemistry.
    DNA Methylation Inhibitor Zebularine Confers Stroke Protection in Ischemic Rats2015In: TRANSLATIONAL STROKE RESEARCH, ISSN 1868-4483, Vol. 6, no 4, p. 296-300Article in journal (Refereed)
    Abstract [en]

    5-Aza-deoxycytidine (5-aza-dC) confers neuroprotection in ischemic mice by inhibiting DNA methylation. Zebularine is another DNA methylation inhibitor, less toxic and more stable in aqueous solutions and, therefore more biologically suitable. We investigated Zebularines effects on brain ischemia in a rat middle cerebral artery occlusion (MCAo) model in order to elucidate its therapeutic potential. Male Wistar wild-type (WT) rats were randomly allocated to three treatment groups, vehicle, Zebularine 100 mu g, and Zebularine 500 mu g. Saline (10 mu L) or Zebularine (10 mu L) was administered intracerebroventricularly 20 min before 45-min occlusion of the middle cerebral artery. Reperfusion was allowed after 45-min occlusion, and the rats were sacrificed at 24-h reperfusion. The brains were removed, sliced, and stained with 2 % 2,3,5-triphenyltetrazolium chloride (TTC) before measuring infarct size. Zebularine (500 mu g) reduced infarct volumes significantly (p less than 0.05) by 61 % from 20.7 +/- 4.2 % in the vehicle treated to 8.1 +/- 1.6 % in the Zebularine treated. Zebularine (100 mu g) also reduced infarct volumes dramatically by 55 to 9.4 +/- 1.2 %. The mechanisms behind this neuroprotection is not yet known, but the results agree with previous studies and support the notion that Zebularine-induced inhibition of DNA methyltransferase ameliorates ischemic brain injury in rats.

  • 25.
    Edvardsson, Maria
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Finspång, Primary Health Care in Finspång.
    Sund-Levander, Märtha
    Linköping University, Department of Medical and Health Sciences, Division of Nursing Science. Linköping University, Faculty of Health Sciences.
    Ernerudh, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Region Östergötland, Center for Diagnostics, Department of Clinical Immunology and Transfusion Medicine. Linköping University, Faculty of Health Sciences.
    Theodorsson, Elvar
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Region Östergötland, Center for Diagnostics, Department of Clinical Chemistry. Linköping University, Faculty of Health Sciences.
    Grodzinsky, Eva
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Health Sciences. Region Östergötland, Local Health Care Services in West Östergötland, Research & Development Unit in Local Health Care. Rättsmedicinalverket, Linköping, Sweden.
    Clinical use of conventional reference intervals in the frail elderly2015In: Journal of Evaluation In Clinical Practice, ISSN 1356-1294, E-ISSN 1365-2753, Vol. 21, no 2, p. 229-235Article in journal (Refereed)
    Abstract [en]

    Rationale, aims and objectives

    Reference intervals provided by the laboratory are commonly established by measuring samples from apparently healthy subjects in the ages 18–65 years, excluding elderly individuals with chronic diseases and medication. The aim of our study was to establish whether current reference intervals for immune parameters and chemical biomarkers are valid for older individuals including those with chronic diseases, so-called frail elderly.

    Methods

    Data from our cohort of 138 non-infected nursing home residents (NHR), mean age 86.8 years, range 80–98, were compared with raw data, as basis for the development of reference intervals, obtained from reference populations, like blood donors (IgA, IgG, IgM, C3 and C4) and from the Nordic Reference Interval Project (NORIP) (alanine aminotransferase, albumin, aspartate aminotransferase, creatinine, gamma-glutamyl transferase, lactate dehydrogenase, phosphate, sodium and urea). Immune parameters were measured by nephelometry and in NORIP the measurements were performed by means of different routine methods, in more than 100 laboratories.

    Results

    Only nine individuals (7%) of NHR were found to be free from chronic disease. C3, C4 (P < 0.001) and IgG levels (P < 0.05) were higher, while IgM levels (P < 0.001) were lower in NHR compared with reference blood donors. Levels of alanine aminotransferase, phosphate (P < 0.001), albumin (P < 0.05) and sodium (P < 0.01) were lower while creatinine and urea levels were higher (P < 0.001) in NHR compared with NORIP subjects.

    Conclusion

    Comparing laboratory results from elderly people with conventional reference intervals can be misleading or even dangerous, as normal conditions may appear pathological, or vice versa and thus lead to unnecessary or even harmful treatment.

  • 26.
    Ehrström, M
    et al.
    Division of Surgery Karolinska Institutet.
    Näslund, E
    Division of Surgery Karolinska Institutet.
    Levin, F
    Division of Surgery Karolinska Institutet.
    Kaur, R
    Department of Neurology GlaxoSmithKline.
    Kirchgessner, A L
    Department of Neurology GlaxoSmithKline.
    Theodorsson, Elvar
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of clinical chemistry. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Chemistry.
    Hellström, P M
    Department of Gastroenterology and Hepatology Karolinska Institutet.
    Pharmacokinetic profile of orexin A and effects on plasma insulin and glucagon in the rat2004In: Regulatory Peptides, ISSN 0167-0115, E-ISSN 1873-1686, Vol. 119, no 3, p. 209-212Article in journal (Refereed)
    Abstract [en]

    Orexin A (OXA) is found in the central nervous system (CNS) and in the gut. Peripheral administration of OXA to rats results in an inhibition of fasting motility. Plasma OXA increases during fasting and central administration of OXA increases food intake. The aim of the present study was to assess the pharmacokinetic profile of OXA and the effect of intravenously (IV) administered OXA on plasma concentrations of insulin and glucagon concentrations. Rats were given OXA IV (100 pmol kg-1 min-1) for time periods of 0, 10, 20, 30 min and for 10, 20, 30 min after ceasing a 30-min infusion. After each time period, rats were then sacrificed and blood obtained. OXA was also administered at increasing doses (0, 100, 300 and 500 pmol kg-1 min-1) for 30 min and blood was obtained. Plasma OXA, insulin and glucagon levels were measured using commercially available radioimmunoassay (RIA) kits. The plasma half-life of OXA was 27.1±9.5 min. Stepwise increasing infusion rates of OXA confirmed a linear concentration-time curve and thus first-order kinetics. Its volume of distribution indicated no binding to peripheral tissues. Plasma glucagon decreased during infusion of OXA, while insulin was unaffected. Plasma OXA was raised fourfold after food intake. Thus, OXA has a longer plasma half-life than many other peptides found in the gut. This needs to be taken into account when assessing effects of OXA on biological parameters after peripheral administration.reserved.

  • 27.
    Eintrei, Christina
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Anaesthesiology. Östergötlands Läns Landsting, Anaesthesiology and Surgical Centre, Department of Intensive Care UHL.
    Bergdahl, Björn
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care. Östergötlands Läns Landsting, Heart Centre, Department of Cardiology.
    Fyrenius, Anna
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Clinical Physiology.
    Hultman, Per
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Molecular and Immunological Pathology. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Pathology and Clinical Genetics.
    Theodorsson, Elvar
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of clinical chemistry. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Chemistry.
    Revising a medical PBL-curriculum - the Linköping strategy2004In: Association for Medical Education in Europe,2004, 2004Conference paper (Other academic)
  • 28.
    El-Nour, H
    et al.
    Karolinska University Hospital.
    Lundeberg, L
    Karolinska University Hospital.
    Boman, A
    Unit of Occupational and Environmental Dermatology.
    Beck, O
    Unit of Clinical Pharmacology.
    Harvima, I T
    Department of Dermatology Kupio University Hospital.
    Theodorsson, Elvar
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of clinical chemistry. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Chemistry.
    Norlind, K
    Karolinska University Hospital.
    Study of innervation, sensory neuropeptides, and serotonin in murine contact allergic skin2005In: Immunopharmacology and immunotoxicology, ISSN 0892-3973, E-ISSN 1532-2513, Vol. 27, no 1, p. 67-76Article in journal (Refereed)
    Abstract [en]

    Density of nerve fibers, axonal growth, calcitonin gene-related peptide (CGRP), and substance P, and serotonin immunoreactivity as well as concentration were all determined in a murine model of contact allergy. Female Balb/c mice were sensitized on the back with oxazolone and 6 days later challenged with the same antigen on the dorsal surface of the ears, while control mice received the vehicle only. Then, 24 hr postchallenge, one ear was processed for immunohistochemical staining, while the other was frozen and processed for gas chromatography-mass spectrometry or radioimmunoassay (RIA). Protein gene product 9.5 (PGP 9.5) positive nerve fibers showed a tendency to increase in inflamed ears versus control ears in epidermis as well as the dermis. Growth-associated protein-43 (GAP-43) positive fibers in the epidermis were increased (p < .01) in inflamed ears, compared with control ears, as was the case for the dermal fibers, indicating increased axonal growth. Total (epidermis and dermis) numbers of CGRP and substance P positive nerve fibers tended to increase in the inflamed skin in contrast to control skin. In contrast, RIA demonstrated a lower (p < .05) concentration of CGRP in the inflamed ears compared with controls and a tendency for substance P to decrease in concentration in eczematous ears versus controls. There was no difference in serotonin concentration, or in the number of serotonin positive mast cells, between the inflamed and control skin, whereas semiquantification of serotonin positive platelets showed an increase in the inflamed (++) compared with control ears (+). Our results indicate that 24 hr after being challenged with the antigen, at the peak of murine skin inflammation, axonal growth, sensory neuropeptides, as well as serotonin may be involved. Copyright © 2005 Taylor & Francis Inc.

  • 29.
    El-Nour, H.
    et al.
    Unit of Dermatology and Venereology, Karolinska University Hospital, Stockholm, Sweden, Unit of Dermatology and Venereology, Karolinska University Hospital, SE-171 76 Stockholm, Sweden.
    Lundeberg, L.
    Unit of Dermatology and Venereology, Karolinska University Hospital, Stockholm, Sweden.
    Boman, A.
    U. of Occup. and Environ. Dermatol., Department of Medicine, Karolinska University Hospital, Stockholm, Sweden.
    Theodorsson, Elvar
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry. Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry.
    Hokfelt, T.
    Hökfelt, T., Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Nordlind, K.
    Unit of Dermatology and Venereology, Karolinska University Hospital, Stockholm, Sweden.
    Galanin expression in a murine model of allergic contact dermatitis2004In: Acta Dermato-Venereologica, ISSN 0001-5555, E-ISSN 1651-2057, Vol. 84, no 6, p. 428-432Article in journal (Refereed)
    Abstract [en]

    Galanin is a neuropeptide widely distributed in the nervous system. The expression of galanin was investigated in murine contact allergy using immunohistochemistry, radioimmunoassay and in situ hybridization. Female BALB/c mice were sensitized with oxazolone and 6 days later challenged on the dorsal surface of ears, while control mice received vehicle. After 24 h, one ear was processed for immunostaining using a biotinylated fluorescence technique, while the other ear was frozen and processed for radioimmunoassay or in situ hybridization. Galanin immunoreactive nerve fibres were more numerous (p < 0.01) in the eczematous compared with control ears. Double-staining with antibody to the nerve fibre marker PGP (protein gene product) 9.5 revealed co-localization of PGP 9.5 and galanin in nerve fibres. Radioimmunoassay demonstrated a decrease (p < 0.04) in galanin concentration in eczematous compared with control ears. Our results suggest a role for galanin in murine contact allergy.

  • 30.
    El-Nour, Husameldin
    et al.
    Unit of Dermatology and Venerology Karolinska Institutet.
    Lundberg, Lena
    Unit of Dermatology and Venerology Karolinska Institutet.
    Boman, Anders
    Unit of Occupational and Environmental Dermatology Karolinska Institutet.
    Theodorsson, Elvar
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of clinical chemistry. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Chemistry.
    Hökfelt, Tomas
    Department of Neuroscience Karolinska Institutet.
    Norlind, Klas
    Unit of Dermatology and Venerology Karolinska Institutet.
    Galanin Expression in a Murine Model of Allergic Contact Dermatitis2004In: Acta Dermato-Venereologica, ISSN 0001-5555, E-ISSN 1651-2057, Vol. 84, p. 428-432Article in journal (Refereed)
  • 31.
    El-Salhy, Magdy
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Gastroenterology and Hepatology. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Tjomsland, Vegard
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Gastroenterology and Hepatology.
    Theodorsson, Elvar
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of clinical chemistry. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Chemistry.
    Effects of triple treatment with octreotide, galanin and serotonin on a human pancreas cancer cell line in xenografts2005In: Histology and Histopathology, ISSN 0213-3911, E-ISSN 1699-5848, Vol. 20, no 3, p. 745-752Article in journal (Refereed)
    Abstract [en]

    Human pancreas cancer cells were implanted s.c. in nude mice. After 11 days, the mice were divided into two groups of 13. The first group received sterile saline solution and the second received triple therapy containing octreotide, galanin and serotonin, 40 μg/kg/day as a continuous i.p. infusion via an implanted osmotic pump for 14 days. Triple therapy prolonged the survival rate of the mice bearing human pancreatic carcinoma. Both the volume and weight of tumours in mice given triple therapy were less than in controls (not statistically significant). The proliferation index and the labelling index for epidermal growth factor (EGF) increased significantly in mice given triple therapy vis-á-vis controls. There was no statistically significant difference between control and treated tumours as regards, apoptotic index, necrosis, or number of tumour blood vessels. The increased survival rate was attributed to the reduced tumour load, since both weight and volume were reduced. It is most probable that octreotide was the responsible agent. Further investigation with single and double combinations of octreotide, galanin and serotonin are needed to identify the cause of increased cell proliferation in tumours subjected to these bioactive substances. Identifying the agent(s) inducing pancreatic cancer cell proliferation may be useful in combining a new treatment, as antagonists to these bioactive substances are available.

  • 32.
    Faresjö, Åshild
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Jullander, Miriam
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Götmalm, Sara
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Theodorsson, Elvar
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Chemistry.
    Higher perceived stress and poorer health reflected in elevated cortisol concentrtions measured in extracts of hair from middle-aged healthy women2014In: BMC Psychology, ISSN 2050-7283, Vol. 2, no 30, p. 1-9Article in journal (Refereed)
    Abstract [en]

    Background

    The prevalence of mental strain and stress has increased in modern societies, resulting in increased public health problems. Stress can be measured either by biomarkers or by self-reports. A new biomarker that measures long-term biological stress is cortisol measured in timed hair extracts. Hair grows at approximately 1 cm per month, and retrospectively reflects average stress levels. However, the plausible relationship between perceived stress and self-reported health and this novel biomarker is yet not firmly established. The objective of this study was to investigate the possible relationship between perceived stress, self-reported health, and cortisol in hair extracts in healthy middle-aged women from two different occupations.

    Method

    A cross-sectional study was conducted in 112 middle-aged women working as nurses or librarians in a county in southeast Sweden. The women were invited to fill in a questionnaire covering stress, health, and life situation. The questionnaire included questions on health and disease symptoms, the Perceived Stress Scale (PSS), and the Hospital Anxiety and Depression (HAD) scale. A piece of hair was cut from the vertex posterior area of the head an analysed by a competitive radioimmunoassay method.

    Results

    Middle-aged women who reported high perceived stress (p = 0.031) or lower health (p = 0.029), or had signs of depressiveness (p = 0.016) had significantly higher cortisol concentrations adjusted for age. There were no significant differences in cortisol in hair concentrations or perceived stress between nurses and librarians. Two women with extremely high cortisol concentrations were considered as outliers, but during the interview at follow-up they reported experiences of serious life events in their work or social life during the retrospective time of the sample taken for cortisol measurement.

    Conclusions

    Higher cortisol concentrations measured in the hair of healthy and working middle-aged women were associated with higher perceived stress and generally poorer health and with depressiveness. These findings lend support to the general applicability of cortisol measured in hair extracts as a biomarker in population-based epidemiological studies.

  • 33.
    Farnebo, Simon
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Surgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Sinnescentrum, Department of Plastic Surgery, Hand surgery UHL.
    Winbladh, Anders
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Zettersten, Erik
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Sandström, Per
    Linköping University, Department of Clinical and Experimental Medicine, Surgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Surgery in Östergötland.
    Gullstrand, P
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Sinnescentrum, Department of Anaesthesiology and Surgery UHL.
    Samuelsson, Anders
    Linköping University, Department of Medical and Health Sciences, Anesthesiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Sinnescentrum, Department of Intensive Care UHL.
    Theodorsson, Elvar
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Chemistry.
    Sjöberg, Folke
    Linköping University, Department of Clinical and Experimental Medicine, Burn Center. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Sinnescentrum, Department of Plastic Surgery, Hand surgery UHL. Östergötlands Läns Landsting, Sinnescentrum, Department of Anaesthesiology and Surgery UHL.
    Urea Clearance: A New Technique Based on Microdialysis to Assess Liver Blood Flow Studied in a Pig Model of Ischemia/Reperfusion2010In: EUROPEAN SURGICAL RESEARCH, ISSN 0014-312X, Vol. 45, no 2, p. 105-112Article in journal (Refereed)
    Abstract [en]

    Delayed detection of ischemia is one of the most feared postoperative complications. Early detection of impaired blood flow and close monitoring of the organ-specific metabolic status may therefore be critical for the surgical outcome. Urea clearance is a new technique for continuous monitoring of alterations in blood flow and metabolic markers with acceptable temporal characteristics. We compare this new microdialysis technique with the established microdialysis ethanol technique to assess hepatic blood flow. Six pigs were used in a liver ischemia/reperfusion injury model. Microdialysis catheters were placed in liver segment IV and all circulation was stopped for 80 min, followed by reperfusion for 220 min. Urea and ethanol clearance was calculated from the dialysate and correlated with metabolic changes. A laser Doppler probe was used as reference of restoration of blood flow. Both urea and ethanol clearance reproducibly depicted changes in liver blood flow in relation to metabolic changes and laser Doppler measurements. The two techniques highly correlated both overall and during the reperfusion phase (r = 0.8) and the changes were paralleled by altered perfusion as recorded by laser Doppler.

  • 34.
    Faxälv, Lars
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Clinical Chemistry.
    Boknäs, Niklas
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences.
    Ström, Jakob
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry. Linköping University, Faculty of Health Sciences.
    Tengvall, Pentti
    University of Gothenburg, Gothenburg, Sweden .
    Theodorsson, Elvar
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Chemistry.
    Ramström, Sofia
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences.
    Lindahl, Tomas
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Clinical Chemistry.
    Putting polyphosphates to the test: evidence against platelet-induced activation of factor XII2013In: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 122, no 23, p. 3818-3824Article in journal (Refereed)
    Abstract [en]

    The recent claim that stimulated platelets activate the intrinsic pathway of coagulation by the release of polyphosphates has been considered a breakthrough in hemostasis research. In little more than 3 years, the original publication by Muller et al has been cited greater than100 times. However, none of the citing articles has sought to independently validate this potentially paradigm-shifting concept. To this end, we performed extensive experimentation in vitro and in vivo in an attempt to verify the claim that factor XII (FXII) is primarily activated by stimulated platelets. In contrast to the original assertion, platelet-derived polyphosphates were found to be weak activators of FXII, with a FXIIa-generating activity of less than10% compared with equivalent concentrations of kaolin. Using different coagulation assays, it was shown that platelet contribution to whole blood coagulation was unrelated to the generation of activated FXII in vitro. Additionally, key results used to verify the hypothesis in the original study in vivo were found to be irreproducible. We conclude that platelet-derived polyphosphates are not physiologically relevant activators of FXII.

  • 35.
    Grip, L
    et al.
    Karolinska Institute, Sweden .
    Lonne-Rahm, S-B
    Karolinska Institute, Sweden .
    Holst, M
    Astrid Lindgren Childrens Hospital, Sweden .
    Johansson, B
    Karolinska Institute, Sweden .
    Nordlind, K
    Karolinska Institute, Sweden .
    Theodorsson, Elvar
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Diagnostics, Department of Clinical Chemistry.
    El-Nour, H
    Karolinska Institute, Sweden .
    Substance P alterations in skin and brain of chronically stressed atopic-like mice2013In: Journal of the European Academy of Dermatology and Venereology, ISSN 0926-9959, E-ISSN 1468-3083, Vol. 27, no 2, p. 199-205Article in journal (Refereed)
    Abstract [en]

    Background Stress is known to worsen the symptoms of atopic eczema (AE). Substance P is likely to play an important role in the development and pathogenesis of AE. less thanbrgreater than less thanbrgreater thanObjective To examine a possible connection between chronic mild stress and changes in the expression of substance P and its receptor (R) neurokinin (NK) 1 in the skin and stress-related brain regions in NC/Nga atopic-like mice. less thanbrgreater than less thanbrgreater thanMethods The mice were divided into three groups (eight animals per group): SE (stressed eczematous), NSE (non-stressed eczematous) and SC (stressed control). Ears and brains of the mice were investigated using immunohistochemistry and RT-PCR. less thanbrgreater than less thanbrgreater thanResults In the skin, there was a decrease in the number of substance P immunoreactive nerve fibres in SE compared with SC group. RT-PCR showed a strong tendency to an increase in mRNA for NK1R in the skin of SE compared with NSE mice. There was an increase in the number of mast cells and the degree of their degranulation in the SE compared with both other groups. less thanbrgreater than less thanbrgreater thanA decrease in substance P immunoreactivity in medial hippocampus was found in SE compared with NSE animals. In prefrontal cortex and central amygdala, there were no significant differences in substance P immunoreactivity between the three groups. less thanbrgreater than less thanbrgreater thanConclusion Exposure to chronic mild stress in NC/Nga atopic-like mice may result in altered expression patterns of substance P in the skin and hippocampus.

  • 36.
    Hannestad, Ulf
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry.
    Theodorsson, Elvar
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Chemistry.
    Evengard, B.
    Evengård, B., Department of Laboratory Medicine, Karolinska Institutet, Karolinska University Hospital, Huddinge, SE-141 86 Stockholm, Sweden.
    ß-Alanine and ?-aminobutyric acid in chronic fatigue syndrome2007In: Clinica Chimica Acta, ISSN 0009-8981, E-ISSN 1873-3492, Vol. 376, no 1-2, p. 23-29Article in journal (Refereed)
    Abstract [en]

    Background: Due to the occurrence of sleep disturbances and fatigue in chronic fatigue syndrome (CFS), an investigation was performed to examine if there is an abnormal excretion of ?-aminobutyric acid (GABA) and/or its structural analogue ß-alanine in the urine from CFS patients. Both GABA and ß-alanine are inhibitory neurotransmitters in the mammalian central nervous system. Methods: The 24 h urine excretion of GABA and ß-alanine was determined by isotope dilution gas chromatography mass spectrometry in 33 CFS patients and 43 healthy controls. The degree of symptoms in both patients and controls was measured by grading of three typical CFS symptoms using a Visual Analogue Scale. Results: Men had a significantly higher excretion of both ß-alanine and GABA than women. Comparing CFS patients with healthy controls showed no significant difference in excretion of neither ß-alanine nor GABA. No correlation was found between the excretion of ß-alanine or GABA and any of the three characteristic CFS symptoms measured. However, two female and two male CFS patients excreted considerably higher amounts of ß-alanine in their 24 h urine samples than control subjects. Conclusions: Increased excretion of ß-alanine was found in a subgroup of CFS patients, indicating that there may be a link between CFS and ß-alanine in some CFS patients. © 2006 Elsevier B.V. All rights reserved.

  • 37.
    Hellström, P. M.
    et al.
    Department of Medicine Karolinska Institutet, Stockholm.
    Näslund, E.
    Deparment of Clinical Sciences, Karolinska Institutet Karolinska Institutet, Stockholm.
    Edholm, T.
    Department of Medicine Karolinska Institutet, Stockholm.
    Schmidt, P. T.
    Department of Medicine Karolinska Institutet, Stockholm.
    Kristensen, J.
    Department of Medicine Karolinska Institutet, Stockholm.
    Theodorsson, Elvar
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Chemistry.
    Holst, J. J.
    §Department of Medical Physiology University of Copenhagen, Denmark.
    Efendic, S.
    Department of Molecular Medicine and Surgery Karolinska Institutet, Stockholm.
    GLP-1 suppresses gastrointestinal motility and inhibits the migrating motor complex in healthy subjects and patients with irritable bowel syndrome2008In: Neurogastroenterology and Motility, ISSN 1350-1925, E-ISSN 1365-2982, Vol. 20, no 6, p. 649-659Article in journal (Refereed)
    Abstract [en]

    Glucagon-like peptide-1 (GLP-1) is released after food intake to act as an incretin. GLP-1 also inhibits gastric emptying and increases satiety. In rats, GLP-1 inhibits small bowel motility. Our aim was to study the effects of GLP-1 on gastrointestinal motility in healthy subjects and patients with irritable bowel syndrome (IBS). Antro-duodeno-jejunal manometry was carried out during a 4-h control period with saline, followed by a 4-h period with intravenous GLP-1 (healthy: 0.7 and 1.2 pmol kg-1 min-1 (n = 16), IBS, 1.2 and 2.5 pmol kg-1 min-1 (n = 14). Plasma was analysed for GLP-1 and gut hormones, and gut tissue expression of GLP-1 receptor was studied. In healthy subjects, GLP-1 0.7 pmol kg-1 min-1 reduced the migrating motor complexes (MMCs) from a median of 2 (range 2-3) to 0.5 (0-2), and motility index from 4.9 ± 0.1 to 4.3 ± 0.3 ln ∑(mmHg*s min-1) in jejunum, while GLP-1 1.2 pmol kg -1 min-1 diminshed MMCs from 2 (2-3) to 1.5 (1-2.5), and motility index from 5.2 ± 0.2 to 4.4 ± 0.2. In IBS patients, GLP-1 1.2 pmol kg-1 min-1 reduced the MMCs from 2.5 (2-3.5) to 1 (0-1.5) without affecting motility index. At 2.5 pmol kg-1 min -1 GLP-1 decreased MMCs from 2 (1.5-3) to 1 (0.5-1.5), and motility index from 5.2 ± 0.2 to 4.0 ± 0.5. Motility responses to GLP-1 were similar in antrum and duodenum. Presence of the GLP-1 receptor in the gut was verified by reverse transcriptase PCR. In conclusion, the gut peptide GLP-1 decreases motility in the antro-duodeno-jejunal region and inhibits the MMC in healthy subjects and IBS patients. © 2008 The Authors.

  • 38.
    Hilke, Susanne
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry.
    Hokfelt, T.
    Hökfelt, T., Department of Neuroscience, Karolinska Institutet, Retzius väg 8, SE-171 77 Stockholm, Sweden.
    Darwish, M.
    Faculty of Veterinary Medicine, Department of Animal Hygiene, Assuit University, Egypt.
    Theodorsson, Elvar
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry. Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry.
    Cholecystokinin levels in the rat brain during the estrous cycle2007In: Brain Research, ISSN 0006-8993, E-ISSN 1872-6240, Vol. 1144, no 1, p. 70-73Article in journal (Refereed)
    Abstract [en]

    Cholecystokinin (CCK) is widely distributed in the brain, and its expression has been shown to be regulated by estrogen. In the present study we used radioimmunoassay to monitor CCK levels in rat brain during a normal estrous cycle. Compared to di-estrous and estrous, CCK-like immunoreactivity was significantly reduced in cingulate and frontal cortex, hippocampus, striatum and hypothalamus during pro-estrous, that is the phase with the highest plasma estradiol levels. These results provide further evidence that circulating steroid hormones in the female rat can influence expression of a brain peptide, in this case CCK, and primarily in the limbic system, which is interesting in the context that CCK has been associated with anxiety and depression in both animals and humans. © 2007 Elsevier B.V. All rights reserved.

  • 39.
    Hilke, Susanne
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry. Linköping University, Faculty of Health Sciences.
    Holm, Lovisa
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry. Linköping University, Faculty of Health Sciences.
    Aman, Katarina
    Karolinska Institute.
    Hokfelt, Tomas
    Karolinska Institute.
    Theodorsson, Elvar
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Chemistry.
    Rapid change of neuropeptide Y levels and gene-expression in the brain of ovariectomized mice after administration of 17 beta-estradiol2009In: NEUROPEPTIDES, ISSN 0143-4179, Vol. 43, no 4, p. 327-332Article in journal (Refereed)
    Abstract [en]

    Estrogen alters excitability and changes synaptic morphology in the rat hippocampal formation. We have compared, by means of radioimmunoassay and in situ hybridization, the effects of short-term treatment with 17 beta-estradiol on neuropeptide Y (NPY) in the brain of ovariectomized mice. A highly significant reduction in concentrations of NPY-like immunoreactivity (LI) was observed in the hippocampal formation, some cortical areas and the caudate nucleus 1 h after administration of 17 beta-estradiol as compared to the control group. In contrast, NPY transcript levels increased in the hippocampal formation (dentate gyrus) and the caudate nucleus, possibly representing a compensatory increase of NPY synthesis following increased estradiol-induced NPY release. These data suggest that 17 beta-estradiol, via membrane-related mechanisms, increases NPY release and synthesis in forebrain areas involved in cognition, mood and motor functions.

  • 40.
    Hilke, Susanne
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry. Linköping University, Faculty of Health Sciences.
    Hökfelt, Tomas
    Department of Neuroscience, Karolinska Institutet, Retzius väg 8, Stockholm, Sweden.
    Theodorsson, Elvar
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Chemistry.
    A short estrogen-responsive N-terminal galanin homologue found in rat brain and gut with antiserum raised against rat galanin(1-16)2007In: Neurochemical Research, ISSN 0364-3190, Vol. 31, no 2, p. 177-188Article in journal (Refereed)
    Abstract [en]

    Galanin-like peptide (GALP) is currently the only known galanin(1-29) homologue. However, three different galanin receptors, of which GalR3 exhibits comparatively low affinity for galanin(1-29), and molecular heterogeneity of immunoreactive galanin are arguments for presence of other endogenous galanin homologues. Since antibodies recognize three-dimensional structures of 3–5 amino acids in a peptide, we raised antibodies in rabbits against galanin(1-16) conjugated to bovine serum albumin, looking for the presence of endogenous N-terminal galanin homologues in rat tissues. The antiserum selected had 7,830 times higher avidity for galanin(1-16) compared to galanin(1-29). A single immunoreactive component with a Stokes radius of about 8 amino acids was found. Immunohistochemistry strongly suggested that this immunoreactivity is localised in the same neurons as galanin(1-29). Furthermore, its concentration was increased in response to estrogen treatment in the same brain regions as galanin(1-29), although not as rapidly. The present results indicate the presence of a novel endogenous N-terminal galanin homologue.

  • 41.
    Hilke, Susanne
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry. Linköping University, Faculty of Health Sciences.
    Theodorsson, Anette
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry. Linköping University, Faculty of Health Sciences.
    Fetissov, Serguei
    Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden .
    Åman, Katarina
    Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden .
    Holm, Lovisa
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry. Linköping University, Faculty of Health Sciences.
    Hökfelt, Tomas
    Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden .
    Theodorsson, Elvar
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry. Linköping University, Faculty of Health Sciences.
    Estrogen induces a rapid increase in galanin levels in female rat hippocampal formation: possibly a nongenomic/indirect effect2005In: European Journal of Neuroscience, ISSN 0953-816X, E-ISSN 1460-9568, Vol. 21, no 8, p. 2089-2099Article in journal (Refereed)
    Abstract [en]

    Administration of 17β-estradiol to ovariectomized rats increased the concentrations of galanin-like immunoreactivity (LI) in the hippocampal formation by 215% (P < 0.001) within 1 h. An increase of 125% (P < 0.05) was observed in the same brain region in the proestrous phase of a normal estrous cycle. Tamoxifen® did not block the 17β-estradiol-induced increase in the concentration of galanin-LI but resulted in a 62% decrease in the hypothalamus within 1 h. In vivo microdialysis in the dorsal hippocampal formation showed a decrease of extracellular galanin-LI (P < 0.001) 1−2 h after treatment with 17β-estradiol, indicating a decreased release of galanin. For comparision, we studied the concentrations of neuropeptide Y, which were not influenced significantly in any of the regions studied. Taken together our results suggest that 17β-estradiol inhibits galanin release, presumably from noradrenergic nerve terminals, and primarily via a nongenomic/indirect action, not necessarily involving the classical nuclear receptors ER-α or ER-β. These rapid estrogen-induced changes in galanin release could influence transmitter signalling and plasticity in the hippocampal formation.

  • 42.
    Hilke, Susanne
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry. Linköping University, Faculty of Health Sciences.
    Theodorsson, Anette
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry. Linköping University, Faculty of Health Sciences.
    Rugarn, Olof
    Hökfelt, Tomas
    Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Theodorsson, Elvar
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry. Linköping University, Faculty of Health Sciences.
    Galanin in the hippocampal formation of female rats: effects of 17beta estradiol2005In: Neuropeptides, ISSN 0143-4179, Vol. 39, no 3, p. 253-257Article in journal (Refereed)
    Abstract [en]

    17β-Estradiol induced an increase in tissue concentrations of galanin in the hippocampal formation of ovariectomized rats. This increase was dose- and time dependent, and occurred already 60 min after steroid administration and was not blocked by Tamoxifen®. There was also an increase in galanin in the pro-estrous phase in regularly cycling rats. The estrogen-induced rapid increase may at least in part be due to decreased release of galanin as demonstrated by in vivo microdialysis studies. Thus, sex steroid hormones may influence signalling molecules in brain areas of importance for cognitive functions.

  • 43.
    Hoe-Hansen, Carsten
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Orthopaedics. Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    Norlin, Rolf
    Linköping University, Department of Clinical and Experimental Medicine, Orthopaedics. Linköping University, Faculty of Health Sciences.
    Theodorsson, Elvar
    Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Chemistry. Linköping University, Faculty of Health Sciences.
    Hildebrand, Claes
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    Acute local inflammation elicits sprouting of sensory axons in the rat supraspinatus tendonManuscript (preprint) (Other academic)
    Abstract [en]

    Inflammation activates nociceptive nerve endings and can elicit local sprouting of axons. We hypothesized that axon sprouting might be one factor behind the emergence of painful inflammatory conditions in the shoulder. Here we examine the distribution of sensory and sympathetic axons in the rat subacromial space under normal conditions and after local induction of inflammation with carrageenan. Furthermore, we measured the neuropeptide content in the supraspinatus tendon. In normal rats protein gene product 9.5- (POP 9.5-), substance P- (SP-), calcitonin gene related peptide- (CGRP-), neuropeptide Y- (NPY-) and tyrosine hydroxylase- (TH-) like immunoreactive (LI) axon profiles occurred in the subacromial space and around the glenohumeral joint. In the supraspinatus tendon axon profiles were limited to the tendon-muscle junction. After carrageenan injection inflammatory cells invaded the tendon and the subacromial bursa with a maximum at 2-3 weeks. Moreover, the tendon and the bursa showed signs of sprouting of PGP-9.5-, SP- and CGRP-LI axons, but not NPY- and TH-LI axons. The tendon was also invaded by blood vessels. The occurrence of axon profiles had a maximum at 2 weeks after injection and then subsided. Also, these axons were GAP-43-LI indicating collateral sprouting of nociceptive nerve fibres. There was no significant increase in the concentration of the neuropeptides SP and CGRP in the supraspinatus tendon. No inflammatory reaction or sprouting of nerve fibres was seen in saline-injected controls. We conclude that an acute inflammation in the subacromial space of the rat shoulder region can elicit a transient local sprouting of sensory axons in the tendon stroma and associated aberrant blood vessels.

  • 44.
    Hoe-Hansen, Carsten
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Orthopaedics. Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    Norlin, Rolf
    Linköping University, Department of Clinical and Experimental Medicine, Orthopaedics. Linköping University, Faculty of Health Sciences.
    Theodorsson, Elvar
    Linköping University, Department of Biomedicine and Surgery, Clinical Chemistry. Linköping University, Faculty of Health Sciences.
    Hildebrand, Claes
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    Increased Occurrence of Nerve Fibres and some Neuropeptides in Subacromial Tissue Biopsies from Patients with Impingement Syndrome of the ShoulderManuscript (preprint) (Other academic)
    Abstract [en]

    Background: The pathophysiology of subacromial inflammation is not fully understood. In the present study we evaluate the presence of sensory and sympathetic nerve fibres and some neuropeptides in biopsies from the supraspinatus tendon and the subacromial bursa of patients with chronic subacromial inflammation as well as of control cases.

    Methods: The occurrence of nerve fibres was subjectively assessed by immunohistochemistry. The concentration of substance P (SP), calcitonin generelated peptide (CGRP) and neuropeptide Y (NPY) was measured by radioimmunoassay (RIA).

    Results: In tendon biopsies from patients with an intact or partially ruptured tendon protein gene product 9.5-like immunoreactive (LI), SP-LI and CGRP-LI nerve fibres were abnormally abundant. In patients with a total tendon rupture nerve fibre occurrence was normal. All biopsies from the bursa exhibited an abnormally high occurrence of SP- and CGRP-LI nerve fibres. In all biopsies the tendon and the bursa contained more blood vessels than normal. The vessels were surrounded by NPY- and tyrosine hydroxylase-LI nerve fibres in a subjectively normal pattern. RIA analysis revealed that the concentration of all three neuropeptides was abnormally high in tendon biopsies from patients with an intact or partially ruptured tendon. Tendon biopsies from patients with total tendon rupture showed statistically normal levels. Biopsies from the bursa showed abnormally high levels of SP and CGRP but normal levels of NPY in all patients.

    Conclusion: We conclude, that the supraspinatus tendon and the subacromial bursa exhibit an increased occurrence of nerve fibres and some neuropeptides in patients with chronic subacromial inflammation.

    Clinical relevance: Patients with chronic subacromial inflammation have a disabling pain problem. The increased local occurrence of sensory andsympathetic axons in the inflamed tissues as well as the elevated tissue concentration of certain neuropeptides may represent important factors behind that problem.

  • 45.
    Holm, Lovisa
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry. Linköping University, Faculty of Health Sciences.
    Hilke, Susanne
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Clinical Chemistry.
    Theodorsson, Elvar
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Chemistry.
    Hokfelt, Tomas
    Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Theodorsson, Annette
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Reconstruction Centre, Department of Neurosurgery UHL.
    Changes in galanin and GalR1 gene expression in discrete brain regions after transient occlusion of the middle cerebral artery in female rats2012In: Neuropeptides, ISSN 0143-4179, E-ISSN 1532-2785, Vol. 46, no 1, p. 19-27Article in journal (Refereed)
    Abstract [en]

    Injury to neurons results in upregulation of galanin in some central and peripheral systems, and it has been suggested that this neuropeptide may play a protective and trophic role, primarily mediated by galanin receptor 2 (GalR2). The objective of the present study was to investigate galanin, GalR1, GalR2 and GalR3 gene expression in the female rat brain seven days after a 60-min unilateral occlusion of the middle cerebral artery followed by reperfusion. Quantitative real-time PCR was employed in punch-biopsies from the locus coeruleus, somatosensory cortex and dorsal hippocampal formation including sham-operated rats as controls. Galanin gene expression showed a ~2.5-fold increase and GalR1 a ~1.5-fold increase in the locus coeruleus of the ischemic hemisphere compared to the control side. Furthermore, the GalR1 mRNA levels decreased by 35% in the cortex of the ischemic hemisphere. The present results indicate that a stroke-induced forebrain lesion upregulates synthesis of galanin and GalR1 in the locus coeruleus, a noradrenergic cell group projecting to many forebrain areas, including cortex and the hippocampal formation. These results support the notion that galanin may play a role in the response of the central nervous system to injury and have trophic eff ects.

  • 46.
    Holm, Lovisa
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry. Linköping University, Faculty of Health Sciences.
    Theodorsson, Elvar
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Chemistry.
    Hokfelt, Tomas
    Karolinska Institute.
    Theodorsson, Annette
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Reconstruction Centre, Department of Neurosurgery UHL.
    Effects of intracerebroventricular galanin or a galanin receptor 2/3 agonist on the lesion induced by transient occlusion of the middle cerebral artery in female rats2011In: Neuropeptides, ISSN 0143-4179, E-ISSN 1532-2785, Vol. 45, no 1, p. 17-23Article in journal (Refereed)
    Abstract [en]

    Several studies have shown that injury to the central and peripheral nervous system can increase expression of galanin, a 29 amino acid neuropeptide. Moreover, there is evidence that galanin, especially through its galanin receptor 2 (GalR2) receptor, plays a neuroprotective role in different injury models. However, direct studies of a possible neuroprotective effect of galanin in experimental stroke models are lacking. Galanin, a GalR2/3 agonist or artificial CSF was continuously infused intracerebroventricularly (i.c.v.) in naive female rats after a 60 min transient and focal occlusion of the middle cerebral artery. The animals were sacrificed, and the ischemic lesion was visualized using 2,3,5-triphenyltetrazolium hydrochloride (TTC) staining. The lesion was 98% larger after i.c.v, administration of the GalR2/3 agonist (2.4 nmol/day) seven days after occlusion compared to artificial CSF (p = 0.023). No statistically significant differences were found after seven days in the groups treated with galanin in three different concentrations (0.24, 2.4 and 24 nmol/day; p = 0.939, 0.715 and 0.977, respectively). There was no difference in the size of the ischemic lesions measured after three days in the galanin-treated group (2.4 nmol/d) compared to artificial CSF (p = 0.925). The present results show, surprisingly, that a GalR2/3 agonist doubled the size of the ischemic lesion. Whether this effect primarily reflects the properties of the current model, species, gender and/or the mode of galanin administration, e.g. causing desensitization, or whether galanin indeed lacks neuroprotective effect of its own, remains to be corroborated.

  • 47. Holmberg, K
    et al.
    Kuteeva, E
    Brumovsky, P
    Kahl, U
    Karlström, H
    Lucas, G A
    Rodriquez, J
    Westerblad, H
    Hilke, Susanne
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of clinical chemistry.
    Theodorsson, Elvar
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of clinical chemistry. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Chemistry.
    Berge, O-G
    Lendahl, U
    Bartfai, T
    Hökfelt, T
    Generation and phenotypic characterization of a galanin overexpressing mouse2005In: Neuroscience, ISSN 0306-4522, E-ISSN 1873-7544, Vol. 133, no 1, p. 59-77Article in journal (Refereed)
    Abstract [en]

    In most parts of the peripheral nervous system galanin is expressed at very low levels. To further understand the functional role of galanin, a mouse overexpressing galanin under the platelet-derived growth factor-B was generated, and high levels of galanin expression were observed in several peripheral tissues and spinal cord. Thus, a large proportion of neurons in autonomic and sensory ganglia were galanin-positive, as were most spinal motor neurons. Strong galanin-like immunoreactivity was also seen in nerve terminals in the corresponding target tissues, including skin, blood vessels, sweat and salivary glands, motor end-plates and the gray matter of the spinal cord. In transgenic superior cervical ganglia around half of all neuron profiles expressed galanin mRNA but axotomy did not cause a further increase, even if mRNA levels were increased in individual neurons. In transgenic dorsal root ganglia galanin mRNA was detected in around two thirds of all neuron profiles, including large ones, and after axotomy the percentage of galanin neuron profiles was similar in overexpressing and wild type mice. Axotomy reduced the total number of DRG neurons less in overexpressing than in wild type mice, indicating a modest rescue effect. Aging by itself increased galanin expression in the superior cervical ganglion in wild type and transgenic mice, and in the latter also in preganglionic cholinergic neurons projecting to the superior cervical ganglion. Galanin overexpressing mice showed an attenuated plasma extravasation, an increased pain response in the formalin test, and changes in muscle physiology, but did not differ from wild type mice in sudomotor function. These findings suggest that overexpressed galanin in some tissues of these mice can be released and via a receptor-mediated action influence pathophysiological processes. © 2005 Published by Elsevier Ltd on behalf of IBRO.

  • 48.
    Ingberg, Edvin
    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, Center for Diagnostics, Department of Clinical Chemistry.
    Dock, Hua
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Chemistry.
    Theodorsson, Elvar
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Chemistry.
    Theodorsson, Annette
    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, Department of Neurosurgery.
    Ström, Jakob O
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Chemistry. Vårdvetenskapligt Forskningscentrum/Centre for Health Sciences, Örebro University Hospital, Region Örebro Län, Örebro, Sweden / School of Health and Medical Sciences, Örebro University, Örebro, Sweden..
    Method parameters’ impact on mortality and variability in mouse stroke experiments: a meta-analysis2016In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 6Article in journal (Refereed)
    Abstract [en]

    Although hundreds of promising substances have been tested in clinical trials, thrombolysis currently remains the only specifi c pharmacological treatment for ischemic stroke. Poor quality, e.g. low statistical power, in the preclinical studies has been suggested to play an important role in these failures. Therefore, it would be attractive to use animal models optimized to minimize unnecessary mortality and outcome variability, or at least to be able to power studies more exactly by predicting variability and mortality given a certain experimental setup. The possible combinations of methodological parameters are innumerous, and an experimental comparison of them all is therefore not feasible. As an alternative approach, we extracted data from 334 experimental mouse stroke articles and, using a hypothesis-driven meta-analysis, investigated the method parameters’ impact on infarct size variability and mortality. The use of Swiss and C57BL6 mice as well as permanent occlusion of the middle cerebral artery rendered the lowest variability of the infarct size while the emboli methods increased variability. The use of Swiss mice increased mortality. Our study offers guidance for researchers striving to optimize mouse stroke models.

  • 49.
    Ingberg, Edvin
    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, Center for Diagnostics.
    Gudjonsdottir, Johanna
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Neurosurgery.
    Theodorsson, Elvar
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Chemistry.
    Theodorsson, Annette
    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, Department of Neurosurgery.
    Ström, Jakob
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. County Council Örebro, Sweden; University of Örebro, Sweden.
    Elevated body swing test after focal cerebral ischemia in rodents: methodological considerations2015In: BMC neuroscience (Online), ISSN 1471-2202, E-ISSN 1471-2202, Vol. 16, no 50Article in journal (Refereed)
    Abstract [en]

    Background: The elevated body swing test (EBST) is a behavioral test used to evaluate experimental stroke in rodents. The basic idea is that when the animal is suspended vertically by the tail, it will swing its head laterally to the left or right depending on lesion side. In a previous study from our lab using the EBST after middle cerebral artery occlusion (MCAo), rats swung contralateral to the infarct day 1 post-MCAo, but ipsilateral day 3 post-MCAo. This shift was unexpected and prompted us to perform the present study. First, the literature was systematically reviewed to elucidate whether a similar shift had been noticed before, and if consensus existed regarding swing direction. Secondly, an experiment was conducted to systematically investigate the suggested behavior. Eighty-three adult male and female Sprague-Dawley rats were subjected to MCAo or sham surgery and the EBST was performed up to 7 days after the lesion. Results: Both experimentally and through systematic literature review, the present study shows that the direction of biased swing activity in the EBST for rodents after cerebral ischemia can differ and even shift over time in some situations. The EBST curve for females was significantly different from that of males after the same occlusion time (p = 0.023). Conclusions: This study highlights the importance of adequate reporting of behavioral tests for lateralization and it is concluded that the EBST cannot be recommended as a test for motor asymmetry after MCAo in rats.

  • 50.
    Ingberg, Edvin
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry. Linköping University, Faculty of Health Sciences.
    Theodorsson, Annette
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry. Linköping University, Department of Clinical and Experimental Medicine, Neurosurgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Department of Neurosurgery.
    Theodorsson, Elvar
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Clinical Chemistry.
    Ström, Jakob O
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry. Linköping University, Faculty of Health Sciences.
    Methods for long-term 17β-estradiol administration to mice2012In: General and Comparative Endocrinology, ISSN 0016-6480, E-ISSN 1095-6840, Vol. 175, no 1, p. 188-193Article in journal (Refereed)
    Abstract [en]

    Rodent models constitute a cornerstone in the elucidation of the effects and biological mechanisms of 17β-estradiol. However, a thorough assessment of the methods for long-term administration of 17β-estradiol to mice is lacking. The fact that 17β-estradiol has been demonstrated to exert different effects depending on dose emphasizes the need for validated administration regimens. Therefore, 169 female C57BL/6 mice were ovariectomized and administered 17β-estradiol using one of the two commonly used subcutaneous methods; slow-release pellets (0.18 mg, 60-day release pellets; 0.72 mg, 90-day release pellets) and silastic capsules (with/without convalescence period, silastic laboratory tubing, inner/outer diameter: 1.575/3.175 mm, filled with a 14 mm column of 36 μg 17β-estradiol/mL sesame oil), or a novel peroral method (56 μg 17β-estradiol/day/kg body weight in the hazelnut cream Nutella). Forty animals were used as ovariectomized and intact controls. Serum samples were obtained weekly for five weeks and 17β-estradiol concentrations were measured using radioimmunoassay. The peroral method resulted in steady concentrations within – except on one occasion – the physiological range and the silastic capsules produced predominantly physiological concentrations, although exceeding the range by maximum a factor three during the first three weeks. The 0.18 mg pellet yielded initial concentrations an order of magnitude higher than the physiological range, which then decreased drastically, and the 0.72 mg pellet produced between 18 and 40 times higher concentrations than the physiological range during the entire experiment. The peroral method and silastic capsules described in this article constitute reliable modes of administration of 17β-estradiol, superior to the widely used commercial pellets.

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