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  • 1. Aalto, Kristiina
    et al.
    Korhonen, Laura
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Neuroscience.
    Lahdenne, Pekka
    Pelkonen, Pirkko
    Lindholm, Dan
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Neuroscience.
    Nerve growth factor in serum of children with systemic lupus erythematosus is correlated with disease activity2002In: Cytokine, Vol. 20, 136- p.Article in journal (Refereed)
  • 2.
    Aanestad, O
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    Flink, R
    Department of Neuroscience.
    Urinary stress incontinence. A urodynamic and quantitative electromyographic study of the perineal muscles.1999In: Acta Obstet. Gynecol. Scand., Vol. 78, 245- p.Article in journal (Refereed)
  • 3.
    Aanestad, Ö
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Neuroscience.
    Flink, R
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Neuroscience.
    Urinary stress incontinence: a urodynamic and quantitative electromyogrpahic study of the perineal muscles.1998In: Acta Obstet. Gynecol. Scand., Vol. 77, 1- p.Article in journal (Refereed)
  • 4. Aanestad, Ö
    et al.
    Flink, R
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Neuroscience.
    Haggman, M
    Department of Surgical Sciences.
    Norlen, BJ
    Department of Surgical Sciences.
    Interference pattern in the urethral sphincter: a quantitative study in patients before and after radical retropubic prostatectomy.1998In: Scand J Urol and Nephrology, Vol. 32, 1- p.Article in journal (Refereed)
  • 5. Aardal-Eriksson, E
    et al.
    Eriksson, T.E
    Holm, A-C
    Lundin, T
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Neuroscience.
    Salivary cortisol and serum prolactin in relation to stress rating scales in a group of rescue workers1999In: Biol. Psychiatry, Vol. 46, 850- p.Article in journal (Refereed)
  • 6.
    Aare, Sudhakar
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Clinical Neurophysiology.
    Ochala, Julien
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Clinical Neurophysiology.
    Norman, Holly S
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Clinical Neurophysiology.
    Radell, Peter
    Eriksson, Lars I
    Göransson, Hanna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Chen, Yi-Wen
    Hoffman, Eric P
    Larsson, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Clinical Neurophysiology.
    Mechanisms underlying the sparing of masticatory versus limb muscle function in an experimental critical illness model2011In: Physiological Genomics, ISSN 1094-8341, E-ISSN 1531-2267, Vol. 43, no 24, 1334-1350 p.Article in journal (Refereed)
    Abstract [en]

    Acute quadriplegic myopathy (AQM) is a common debilitating acquired disorder in critically ill intensive care unit (ICU) patients which is characterized by tetraplegia/generalized weakness of limb and trunk muscles. Masticatory muscles, on the other hand, are typically spared or less affected, yet the mechanisms underlying this striking muscle-specific difference remain unknown. This study aims to evaluate physiological parameters and the gene expression profiles of masticatory and limb muscles exposed to factors suggested to trigger AQM, such as mechanical ventilation, immobilization, neuromuscular blocking agents (NMBA), corticosteroids (CS) and sepsis for five days by using a unique porcine model mimicking the ICU conditions. Single muscle fiber cross-sectional area and force-generating capacity, i.e., maximum force normalized to fiber cross-sectional area (specific force), revealed maintained masseter single muscle fiber cross-sectional area and specific-force after five days exposure to all triggering factors. This is in sharp contrast to observations in limb and trunk muscles, showing a dramatic decline in specific force in response to five days exposure to the triggering factors. Significant differences in gene expression were observed between craniofacial and limb muscles, indicating a highly complex and muscle specific response involving transcription and growth factors, heat shock proteins, matrix metalloproteinase inhibitor, oxidative stress responsive elements and sarcomeric proteins underlying the relative sparing of cranial versus spinal nerve innervated muscles during exposure to the ICU intervention.

  • 7.
    Aare, Sudhakar
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Clinical Neurophysiology.
    Radell, Peter
    Department of anesthesiology, Karolinska Inistitute.
    Eriksson, Lars
    Department of anesthesiology, Karolinska Inistitute.
    Akkad, Hazem
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Clinical Neurophysiology.
    Chen, Yi-Wen
    Research center for genetic medicine.
    Hoffman, Eric
    Research center for genetic medicine.
    Lars, Larsson
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Clinical Neurophysiology.
    Effects of corticosteroids in the development of limb muscle weakness in a porcine intensive care unit model2013In: Physiological Genomics, ISSN 1094-8341, E-ISSN 1531-2267, Vol. 45, no 8, 312-320 p.Article in journal (Refereed)
    Abstract [en]

    Severe muscle wasting is a debilitating condition in critically ill intensive care unit (ICU) patients, characterized by general muscle weakness and dysfunction, resulting in a prolonged mobilization, delayed weaning from the ventilator and a decreased quality of life post-ICU. The mechanisms underlying limbmuscle weakness in ICU patients are complex and involve the impact of primary disease, but also factors common to critically ill ICU patients such as sepsis, mechanical ventilation (MV), immobilization and systemic administration of corticosteroids (CS).  These factors may have additive negative effects on skeletal muscle structure and function, but their respective role alone remain unknown. The primary aim of this study was to examine how CS administration potentiates ventilator and immobilization-related limb muscle dysfunction at the gene level. Comparing biceps femoris gene expression in pigs exposed to MV and CS for five days with only MV pigs for the same duration of time showed a distinct deregulation of 186 genes using microarray. Surprisingly, the decreased force-generation capacity at the single muscle fiber reported in response to the addition of CS administration in mechanically ventilated and immobilized pigs was not associated with an additional up-regulation of proteolytic pathways. On the other hand, an altered expression of genes regulating kinase activity, cell cycle, transcription, channel regulation, oxidative stress response , cytoskeletal, sarcomeric and heat shock protein as well as protein synthesis at the translational level appear to play an additive deleterious role for the  limb muscle weakness in immobilized ICU patients.

     

  • 8.
    Aare, Sudhakar
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Clinical Neurophysiology.
    Radell, Peter
    Department of anesthesiology, Karolinska Inistitute.
    Eriksson, Lars
    Department of anesthesiology, Karolinska Inistitute.
    Chen, Yi-Wen
    Research center for genetic medicine.
    Hoffman, Eric P
    Research center for genetic medicine.
    Larsson, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Clinical Neurophysiology.
    The role of sepsis in the development of limb muscle weakness in a porcine intensive care unit model2012In: Physiological Genomics, ISSN 1094-8341, E-ISSN 1531-2267, Vol. 44, no 18, 865-877 p.Article in journal (Refereed)
    Abstract [en]

    Severe muscle wasting and loss of muscle function in critically ill mechanically ventilated intensive care unit (ICU) patients have significant negative consequences on their recovery and rehabilitation that persist long after their hospital discharge; moreover the underlying mechanisms are unclear. Mechanical ventilation (MV) and immobilization-induced modifications play an important role in these consequences, including endotoxin induced sepsis. The present study aims to investigate how sepsis aggravates ventilator and immobilization-related limb muscle dysfunction. Hence, biceps femoris muscle gene expression was investigated in pigs exposed to ICU intervention, i.e., immobilization, sedation, and MV, alone or in combination with sepsis for five days. In previous studies, we have shown that ICU intervention alone or in combination with sepsis did not affect muscle fiber size on day 5, but a significant decrease was observed in single fiber maximal force normalized to cross-sectional area (specific force) when sepsis was added to the ICU intervention. According to microarray data, the addition of sepsis to the ICU intervention induced a deregulation of more than 500 genes, such as an increased expression of genes involved in chemokine activity, kinase activity and transcriptional regulation. Genes involved in the regulation of the oxidative stress response, cytoskeletal/sarcomeric and heat shock proteins were on the other hand down-regulated when sepsis was added to the ICU intervention. Thus, sepsis has a significant negative effect on muscle function in critically ill ICU patients and chemokine activity and heat shock protein genes are forwarded to play an instrumental role in this specific muscle wasting condition.

  • 9.
    Aare, Sudhakar Reddy
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Clinical Neurophysiology.
    Intensive Care Unit Muscle Wasting: Skeletal Muscle Phenotype and Underlying Molecular Mechanisms2012Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Acute quadriplegic myopathy (AQM), or critical illness myopathy, is a common debilitating acquired disorder in critically ill intensive care unit (ICU) patients characterized by generalized muscle wasting and weakness of limb and trunk muscles. A preferential loss of the thick filament protein myosin is considered pathognomonic of this disorder, but the myosin loss is observed relatively late during the disease progression. In attempt to explore the potential role of factors considered triggering AQM in sedated mechanically ventilated (MV) ICU patients, we have studied the early effects, prior to the myosin loss, of neuromuscular blockade (NMB), corticosteroids (CS) and sepsis separate or in combination in a porcine experimental ICU model. Specific interest has been focused on skeletal muscle gene/protein expression and regulation of muscle contraction at the muscle fiber level. This project aims at improving our understanding of the molecular mechanisms underlying muscle specific differences in response to the ICU intervention and the role played by the different triggering factors.

    The sparing of masticatory muscle fiber function was coupled to an up-regulation of heat shock protein genes and down-regulation of myostatin are suggested to be key factors in the relative sparing of masticatory muscles. Up-regulation of chemokine activity genes and down-regulation of heat shock protein genes play a significant role in the limb muscle dysfunction associated with sepsis. The effects of corticosteroids in the development of limb muscle weakness reveals up-regulation of kinase activity and transcriptional regulation genes and the down-regulation of heat shock protein, sarcomeric, cytoskeletal and oxidative stress responsive genes. In contrast to limb and craniofacial muscles, the respiratory diaphragm muscle responded differently to the different triggering factors. MV itself appears to play a major role for the diaphragm muscle dysfunction. By targeting these genes, future experiments can give an insight into the development of innovative treatments expected at protecting muscle mass and function in critically ill ICU patients.

    List of papers
    1. Mechanisms underlying the sparing of masticatory versus limb muscle function in an experimental critical illness model
    Open this publication in new window or tab >>Mechanisms underlying the sparing of masticatory versus limb muscle function in an experimental critical illness model
    Show others...
    2011 (English)In: Physiological Genomics, ISSN 1094-8341, E-ISSN 1531-2267, Vol. 43, no 24, 1334-1350 p.Article in journal (Refereed) Published
    Abstract [en]

    Acute quadriplegic myopathy (AQM) is a common debilitating acquired disorder in critically ill intensive care unit (ICU) patients which is characterized by tetraplegia/generalized weakness of limb and trunk muscles. Masticatory muscles, on the other hand, are typically spared or less affected, yet the mechanisms underlying this striking muscle-specific difference remain unknown. This study aims to evaluate physiological parameters and the gene expression profiles of masticatory and limb muscles exposed to factors suggested to trigger AQM, such as mechanical ventilation, immobilization, neuromuscular blocking agents (NMBA), corticosteroids (CS) and sepsis for five days by using a unique porcine model mimicking the ICU conditions. Single muscle fiber cross-sectional area and force-generating capacity, i.e., maximum force normalized to fiber cross-sectional area (specific force), revealed maintained masseter single muscle fiber cross-sectional area and specific-force after five days exposure to all triggering factors. This is in sharp contrast to observations in limb and trunk muscles, showing a dramatic decline in specific force in response to five days exposure to the triggering factors. Significant differences in gene expression were observed between craniofacial and limb muscles, indicating a highly complex and muscle specific response involving transcription and growth factors, heat shock proteins, matrix metalloproteinase inhibitor, oxidative stress responsive elements and sarcomeric proteins underlying the relative sparing of cranial versus spinal nerve innervated muscles during exposure to the ICU intervention.

    National Category
    Neurology
    Identifiers
    urn:nbn:se:uu:diva-164317 (URN)10.1152/physiolgenomics.00116.2011 (DOI)000298403600002 ()22010006 (PubMedID)
    Available from: 2011-12-19 Created: 2011-12-19 Last updated: 2017-12-08Bibliographically approved
    2. The role of sepsis in the development of limb muscle weakness in a porcine intensive care unit model
    Open this publication in new window or tab >>The role of sepsis in the development of limb muscle weakness in a porcine intensive care unit model
    Show others...
    2012 (English)In: Physiological Genomics, ISSN 1094-8341, E-ISSN 1531-2267, Vol. 44, no 18, 865-877 p.Article in journal (Refereed) Published
    Abstract [en]

    Severe muscle wasting and loss of muscle function in critically ill mechanically ventilated intensive care unit (ICU) patients have significant negative consequences on their recovery and rehabilitation that persist long after their hospital discharge; moreover the underlying mechanisms are unclear. Mechanical ventilation (MV) and immobilization-induced modifications play an important role in these consequences, including endotoxin induced sepsis. The present study aims to investigate how sepsis aggravates ventilator and immobilization-related limb muscle dysfunction. Hence, biceps femoris muscle gene expression was investigated in pigs exposed to ICU intervention, i.e., immobilization, sedation, and MV, alone or in combination with sepsis for five days. In previous studies, we have shown that ICU intervention alone or in combination with sepsis did not affect muscle fiber size on day 5, but a significant decrease was observed in single fiber maximal force normalized to cross-sectional area (specific force) when sepsis was added to the ICU intervention. According to microarray data, the addition of sepsis to the ICU intervention induced a deregulation of more than 500 genes, such as an increased expression of genes involved in chemokine activity, kinase activity and transcriptional regulation. Genes involved in the regulation of the oxidative stress response, cytoskeletal/sarcomeric and heat shock proteins were on the other hand down-regulated when sepsis was added to the ICU intervention. Thus, sepsis has a significant negative effect on muscle function in critically ill ICU patients and chemokine activity and heat shock protein genes are forwarded to play an instrumental role in this specific muscle wasting condition.

    Keyword
    Sepsis, porcine, muscle wasting, intensive care
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:uu:diva-180380 (URN)10.1152/physiolgenomics.00031.2012 (DOI)000309109100001 ()
    Available from: 2012-09-05 Created: 2012-09-05 Last updated: 2017-12-07Bibliographically approved
    3. Effects of corticosteroids in the development of limb muscle weakness in a porcine intensive care unit model
    Open this publication in new window or tab >>Effects of corticosteroids in the development of limb muscle weakness in a porcine intensive care unit model
    Show others...
    2013 (English)In: Physiological Genomics, ISSN 1094-8341, E-ISSN 1531-2267, Vol. 45, no 8, 312-320 p.Article in journal (Refereed) Published
    Abstract [en]

    Severe muscle wasting is a debilitating condition in critically ill intensive care unit (ICU) patients, characterized by general muscle weakness and dysfunction, resulting in a prolonged mobilization, delayed weaning from the ventilator and a decreased quality of life post-ICU. The mechanisms underlying limbmuscle weakness in ICU patients are complex and involve the impact of primary disease, but also factors common to critically ill ICU patients such as sepsis, mechanical ventilation (MV), immobilization and systemic administration of corticosteroids (CS).  These factors may have additive negative effects on skeletal muscle structure and function, but their respective role alone remain unknown. The primary aim of this study was to examine how CS administration potentiates ventilator and immobilization-related limb muscle dysfunction at the gene level. Comparing biceps femoris gene expression in pigs exposed to MV and CS for five days with only MV pigs for the same duration of time showed a distinct deregulation of 186 genes using microarray. Surprisingly, the decreased force-generation capacity at the single muscle fiber reported in response to the addition of CS administration in mechanically ventilated and immobilized pigs was not associated with an additional up-regulation of proteolytic pathways. On the other hand, an altered expression of genes regulating kinase activity, cell cycle, transcription, channel regulation, oxidative stress response , cytoskeletal, sarcomeric and heat shock protein as well as protein synthesis at the translational level appear to play an additive deleterious role for the  limb muscle weakness in immobilized ICU patients.

     

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:uu:diva-180375 (URN)10.1152/physiolgenomics.00123.2012 (DOI)000317662000002 ()23429211 (PubMedID)
    Available from: 2012-09-05 Created: 2012-09-05 Last updated: 2017-12-07Bibliographically approved
    4. Diaphragm muscle weakness in an experimental porcine intensive care unit model
    Open this publication in new window or tab >>Diaphragm muscle weakness in an experimental porcine intensive care unit model
    Show others...
    2011 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 6, no 6, e20558Article in journal (Refereed) Published
    Abstract [en]

    In critically ill patients, mechanisms underlying diaphragm muscle remodeling and resultant dysfunction contributing to weaning failure remain unclear. Ventilator-induced modifications as well as sepsis and administration of pharmacological agents such as corticosteroids and neuromuscular blocking agents may be involved. Thus, the objective of the present study was to examine how sepsis, systemic corticosteroid treatment (CS) and neuromuscular blocking agent administration (NMBA) aggravate ventilator-related diaphragm cell and molecular dysfunction in the intensive care unit. Piglets were exposed to different combinations of mechanical ventilation and sedation, endotoxin-induced sepsis, CS and NMBA for five days and compared with sham-operated control animals. On day 5, diaphragm muscle fibre structure (myosin heavy chain isoform proportion, cross-sectional area and contractile protein content) did not differ from controls in any of the mechanically ventilated animals. However, a decrease in single fibre maximal force normalized to cross-sectional area (specific force) was observed in all experimental piglets. Therefore, exposure to mechanical ventilation and sedation for five days has a key negative impact on diaphragm contractile function despite a preservation of muscle structure. Post-translational modifications of contractile proteins are forwarded as one probable underlying mechanism. Unexpectedly, sepsis, CS or NMBA have no significant additive effects, suggesting that mechanical ventilation and sedation are the triggering factors leading to diaphragm weakness in the intensive care unit.

    National Category
    Physiology
    Research subject
    Clinical Neurophysiology
    Identifiers
    urn:nbn:se:uu:diva-155622 (URN)10.1371/journal.pone.0020558 (DOI)000291730000014 ()21698290 (PubMedID)
    Available from: 2011-06-27 Created: 2011-06-27 Last updated: 2018-01-12Bibliographically approved
  • 10.
    Abbaspour, Kristina
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Physiotheraphy.
    Lindén, Charlotta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Physiotheraphy.
    Primärvårdsjukgymnastens yrkesroll och kompetens, nu och i framtiden.2010Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
  • 11. Abbott, GW
    et al.
    Mercer, EA
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Neuroscience.
    Miller, RT
    Ramesh, B
    Srai, SK
    Conformational changes in a mammalian voltage-dependent potassium channel inactivation peptide1998In: Biochemistry, Vol. 37, 1640- p.Article in journal (Refereed)
  • 12. Abelson, K.
    et al.
    Jacobsen, K. R.
    Kalliokoski, O.
    Teilmann, C.
    Sundbom, Renée
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Comparative Medicine.
    Hau, J.
    Limitations of the Usefulness of Fecal Corticosterone as Biomarker for Stress in Mice2012In: Journal of the American Association for Laboratory Animal Science, ISSN 1559-6109, Vol. 51, no 5, 639-639 p.Article in journal (Refereed)
  • 13.
    Abelson, Klas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Acetylcholine in Spinal Pain Modulation: An in vivo Study in the Rat2005Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The spinal cord is an important component in the processing and modulation of painful stimuli. Nerve signals from the periphery are relayed and further conducted to the brain (nociception) in the spinal cord, and the most essential modulation of painful information (antinociception) occurs here. Several neurotransmitters are involved in spinal pain modulation, among them acetylcholine. However, the role of acetylcholine has previously been little investigated.

    In the present thesis, the acetylcholine release in the spinal cord was studied in vivo. By using spinal microdialysis on anaesthetised rats, the effects on the intraspinal acetylcholine release of various receptor ligands and analgesic agents were examined. This, together with pain behavioural tests and in vitro pharmacological assays, was used to evaluate the role of acetylcholine in spinal pain modulation. The four studies in this thesis resulted in the following conclusions:

    An increased release of spinal acetylcholine is associated with an elevated pain threshold, while a decreased acetylcholine release is associated with hyperalgesia, as seen after systemic treatment with a muscarinic agonist and an antagonist.

    Lidocaine is a potent analgesic when given systemically. It was found to produce an increase of intraspinal acetylcholine after intravenous injection of analgesic doses. This effect was attenuated after muscarinic, and abolished after nicotinic, receptor blockade.

    Various a2-adrenergic ligands, associated with nociceptive or antinociceptive effects, were found to affect intraspinal acetylcholine release via action on nicotinic receptors.

    Finally, the involvement of spinal acetylcholine in the analgesic effects of aspirin and paracetamol was examined. It was found that spinal acetylcholine could participate in the analgesic effects of aspirin, but not of paracetamol.

    The present thesis provides data that clearly demonstrate a relationship between intraspinal acetylcholine and antinociception, and elucidate interactions between acetylcholine and other mechanisms that mediate antinociception in the spinal cord.

    List of papers
    1. Intravenously administered oxotremorine and atropine, in doses known to affect pain threshold, affect the intraspinal release of acetylcholine in rats
    Open this publication in new window or tab >>Intravenously administered oxotremorine and atropine, in doses known to affect pain threshold, affect the intraspinal release of acetylcholine in rats
    2002 (English)In: Pharmacology and Toxicology, ISSN 0901-9928, E-ISSN 1600-0773, Vol. 90, no 4, 187-192 p.Article in journal (Refereed) Published
    Abstract [en]

    Abstract:Both systemically and intrathecally administered cholinergic agonists produce antinociception while cholinergic antagonists decrease pain threshold. The mechanism and the site of action of these substances are not known. In the present study it was hypothesized that systemically administered muscarinic agonists and antagonists modify nociceptive threshold by affecting intraspinal release of acetylcholine (ACh). Catheters were inserted into the femoral vein in rats maintained on isoflurane anaesthesia for administration of oxotremorine (10–300 μg/kg) and atropine (0.1, 10, 5000 μg/kg). Spinal microdialysis probes were placed intraspinally at approximately the C2–C5 spinal level for sampling of acetylcholine and dialysis delivery of atropine (0.1, 1, 10 nM). Additionally, the tail-flick behaviour was tested on conscious rats injected intraperitoneally with saline, atropine (10, 100 and 5000 μg/kg), or subcutaneously with oxotremorine (30, 100, 300 μg/kg). Subcutaneous administration of oxotremorine (30, 100, 300 μg/kg) significantly increased the tail-flick latency. These doses of oxotremorine dose-dependently increased the intraspinal release of acetylcholine. Intravenously administered atropine, in a dose that produced hyperalgesia (5000 μg/kg) in the tail-flick test, significantly decreased the intraspinal release of acetylcholine. Our results suggest an association between pain threshold and acetylcholine release in spinal cord. It is also suggested that an approximately 30% increase in basal ACh release produces antinociception and that a 30% decrease in basal release produces hyperalgesia.

    Place, publisher, year, edition, pages
    Blackwell, 2002
    National Category
    Biomedical Laboratory Science/Technology
    Identifiers
    urn:nbn:se:uu:diva-7215 (URN)10.1034/j.1600-0773.2002.900403.x (DOI)
    Available from: 2006-10-18 Created: 2006-10-18 Last updated: 2017-12-14Bibliographically approved
    2. Intravenously administered lidocaine in therapeutic doses increases the intraspinal release of acetylcholine in rats
    Open this publication in new window or tab >>Intravenously administered lidocaine in therapeutic doses increases the intraspinal release of acetylcholine in rats
    2002 (English)In: Neuroscience Letters, ISSN 0304-3940, E-ISSN 1872-7972, Vol. 317, no 2, 93-6 p.Article in journal (Refereed) Published
    Abstract [en]

    The local anesthetic lidocaine suppresses different pain conditions when administered systemically. Part of the antinociceptive effect appears to be mediated via receptor mechanisms. We have previously shown that muscarinic and nicotinic agonists that produce antinociception increase the intraspinal release of acetylcholine. In the present study it was hypothesized that systemically administered lidocaine is acting through the same mechanisms as cholinergic agonists and affects the intraspinal release of acetylcholine. Microdialysis probes were placed in anesthetized rats for sampling of acetylcholine. Ten and 30 mg/kg lidocaine injected intravenously significantly increased the intraspinal release of acetylcholine. The effect of lidocaine could be reduced by pretreatment with intraspinally administered atropine or mecamylamine. Our results suggest that the antinociceptive effect produced by systemically administered lidocaine is mediated through an action on muscarinic and nicotinic receptors.

    Place, publisher, year, edition, pages
    Elsevier, 2002
    Keyword
    Lidocaine; Spinal cord; Pain; Microdialysis; Acetylcholine; Muscarinic; Nicotinic
    National Category
    Biomedical Laboratory Science/Technology
    Identifiers
    urn:nbn:se:uu:diva-7227 (URN)10.1016/S0304-3940(01)02440-5 (DOI)
    Available from: 2006-10-24 Created: 2006-10-24 Last updated: 2017-12-14Bibliographically approved
    3. The effects of the alpha2-adrenergic receptor agonists clonidine and rilmenidine, and antagonists yohimbine and efaroxan, on the spinal cholinergic receptor system in the rat
    Open this publication in new window or tab >>The effects of the alpha2-adrenergic receptor agonists clonidine and rilmenidine, and antagonists yohimbine and efaroxan, on the spinal cholinergic receptor system in the rat
    2004 (English)In: Basic & Clinical Pharmacology & Toxicology, ISSN 1742-7835, E-ISSN 1742-7843, Vol. 94, no 4, 153-60 p.Article in journal (Refereed) Published
    Abstract [en]

    Cholinergic agonists produce spinal antinociception via mechanisms involving an increased release of intraspinalacetylcholine. The cholinergic receptor system interacts with several other receptor types, such as a2-adrenergic receptors.To fully understand these interactions, the effects of various receptor ligands on the cholinergic system must be investigatedin detail. This study was initiated to investigate the effects of the a2-adrenergic receptor agonists clonidine and rilmenidineand the a2-adrenergic receptor antagonists yohimbine and efaroxan on spinal cholinergic receptors in the rat. Spinalmicrodialysis was used to measure in vivo changes of acetylcholine after administration of the ligands, with or withoutnicotinic receptor blockade. In addition, in vitro binding properties of the ligands on muscarinic and nicotinic receptorswere investigated. It was found that clonidine and rilmenidine increased, while yohimbine decreased spinal acetylcholinerelease. Efaroxan affected acetylcholine release differently depending on concentration. Nicotinic receptor blockade atten-uated the effect of all ligands. All ligands showed poor binding affinity for muscarinic receptors. On the other hand, allligands possessed affinity for nicotinic receptors. Clonidine and yohimbine binding was best fit to a one site binding curveand rilmenidine and efaroxan to a two site binding curve. The present study demonstrates that the tested a2-adrenergicreceptor ligands affect intraspinal acetylcholine release in the rat evoked by nicotinic receptor mechanisms in vivo, andthat they possess binding affinity to nicotinic receptors in vitro. The binding of a2-adrenergic receptor ligands to nicotinicreceptors might affect the intraspinal release of acetylcholine.

    Place, publisher, year, edition, pages
    Blackwell, 2004
    National Category
    Biomedical Laboratory Science/Technology
    Identifiers
    urn:nbn:se:uu:diva-92739 (URN)10.1111/j.1742-7843.2004.pto940401.x (DOI)15078339 (PubMedID)
    Available from: 2005-03-30 Created: 2005-03-30 Last updated: 2017-12-14Bibliographically approved
    4. Spinal cholinergic involvement after treatment with aspirin and paracetamol in rats
    Open this publication in new window or tab >>Spinal cholinergic involvement after treatment with aspirin and paracetamol in rats
    2004 In: Neurosci. Lett., ISSN 0304-3940, Vol. 368, no 1, 116-120 p.Article in journal (Refereed) Published
    Identifiers
    urn:nbn:se:uu:diva-92740 (URN)
    Available from: 2005-03-30 Created: 2005-03-30Bibliographically approved
  • 14.
    Abelson, Klas
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Comparative Medicine.
    Adem, Bashir
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Comparative Medicine.
    Royo, Felix
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Comparative Medicine.
    Carlsson, Hans-Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Comparative Medicine.
    Hau, Jann
    High plasma corticosterone levels persist during frequent automatic blood sampling in rats2005In: In Vivo, ISSN 0258-851X, E-ISSN 1791-7549, Vol. 19, no 5, 815-19 p.Article in journal (Refereed)
    Abstract [en]

    Corticosterone levels in blood may be used as a marker of stress in rodents, provided that the blood sampling procedure itself is non-stressful. Automated blood sampling equipment (Accusampler®) allows blood sampling without any interference with the animal and might be useful as a tool for an on-line measurement of stress markers in blood. However, the impact of the blood sampling itself on the corticosterone levels in blood is unknown. The present study was designed to evaluate whether the frequency of blood sampling influences the plasma corticosterone levels in male and female rats. During anaesthesia, a catheter was placed in the jugular vein and attached to an Accusampler®. Blood samples (200 μl) were withdrawn with a high (24 samples) or low frequency (3 samples) during a six-hour period immediately after the catheter insertion. The corticosterone levels in the plasma were quantified with ELISA. The corticosterone levels persisted at high post-operation concentrations when blood was collected frequently, while the levels steadily declined significantly during low-frequency sampling. The corticosterone levels were higher in female than in male rats, but the curves were similar. The present study elucidates the importance of considering the frequency of blood withdrawal during automated blood sampling. This parameter may have an impact on the experimental results when using blood corticosterone levels as a stress marker, but also during any in vivo study where blood is collected, since high corticosterone levels may affect the normal physiology of the animals.

  • 15.
    Abelson, Klas
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Comparative Medicine.
    Hau, Jann
    Carlsson, Hans-Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Comparative Medicine.
    Undergraduate and postgraduate students' responses to mandatory courses (FELASA category C) in laboratory animal science 1997-20032005In: Internationalisation and Harmonisation of Laboratory Animal Care and Use Issues: Proceedings of the Ninth FELASA Symposium 14-17 June 2004, Nantes, France / [ed] M. R. Gamble, 2005Conference paper (Other academic)
  • 16.
    Abelson, Klas
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Comparative Medicine.
    Höglund, Urban
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Comparative Medicine.
    Intravenously administered lidocaine in therapeutic doses increases the intraspinal release of acetylcholine in rats2002In: Neuroscience Letters, ISSN 0304-3940, E-ISSN 1872-7972, Vol. 317, no 2, 93-6 p.Article in journal (Refereed)
    Abstract [en]

    The local anesthetic lidocaine suppresses different pain conditions when administered systemically. Part of the antinociceptive effect appears to be mediated via receptor mechanisms. We have previously shown that muscarinic and nicotinic agonists that produce antinociception increase the intraspinal release of acetylcholine. In the present study it was hypothesized that systemically administered lidocaine is acting through the same mechanisms as cholinergic agonists and affects the intraspinal release of acetylcholine. Microdialysis probes were placed in anesthetized rats for sampling of acetylcholine. Ten and 30 mg/kg lidocaine injected intravenously significantly increased the intraspinal release of acetylcholine. The effect of lidocaine could be reduced by pretreatment with intraspinally administered atropine or mecamylamine. Our results suggest that the antinociceptive effect produced by systemically administered lidocaine is mediated through an action on muscarinic and nicotinic receptors.

  • 17.
    Abelson, Klas
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Comparative Medicine.
    Höglund, Urban
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Comparative Medicine.
    Intravenously administered oxotremorine and atropine, in doses known to affect pain threshold, affect the intraspinal release of acetylcholine in rats2002In: Pharmacology and Toxicology, ISSN 0901-9928, E-ISSN 1600-0773, Vol. 90, no 4, 187-192 p.Article in journal (Refereed)
    Abstract [en]

    Abstract:Both systemically and intrathecally administered cholinergic agonists produce antinociception while cholinergic antagonists decrease pain threshold. The mechanism and the site of action of these substances are not known. In the present study it was hypothesized that systemically administered muscarinic agonists and antagonists modify nociceptive threshold by affecting intraspinal release of acetylcholine (ACh). Catheters were inserted into the femoral vein in rats maintained on isoflurane anaesthesia for administration of oxotremorine (10–300 μg/kg) and atropine (0.1, 10, 5000 μg/kg). Spinal microdialysis probes were placed intraspinally at approximately the C2–C5 spinal level for sampling of acetylcholine and dialysis delivery of atropine (0.1, 1, 10 nM). Additionally, the tail-flick behaviour was tested on conscious rats injected intraperitoneally with saline, atropine (10, 100 and 5000 μg/kg), or subcutaneously with oxotremorine (30, 100, 300 μg/kg). Subcutaneous administration of oxotremorine (30, 100, 300 μg/kg) significantly increased the tail-flick latency. These doses of oxotremorine dose-dependently increased the intraspinal release of acetylcholine. Intravenously administered atropine, in a dose that produced hyperalgesia (5000 μg/kg) in the tail-flick test, significantly decreased the intraspinal release of acetylcholine. Our results suggest an association between pain threshold and acetylcholine release in spinal cord. It is also suggested that an approximately 30% increase in basal ACh release produces antinociception and that a 30% decrease in basal release produces hyperalgesia.

  • 18.
    Abelson, Klas
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Comparative Medicine.
    Höglund, Urban
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Comparative Medicine.
    The effects of the alpha2-adrenergic receptor agonists clonidine and rilmenidine, and antagonists yohimbine and efaroxan, on the spinal cholinergic receptor system in the rat2004In: Basic & Clinical Pharmacology & Toxicology, ISSN 1742-7835, E-ISSN 1742-7843, Vol. 94, no 4, 153-60 p.Article in journal (Refereed)
    Abstract [en]

    Cholinergic agonists produce spinal antinociception via mechanisms involving an increased release of intraspinalacetylcholine. The cholinergic receptor system interacts with several other receptor types, such as a2-adrenergic receptors.To fully understand these interactions, the effects of various receptor ligands on the cholinergic system must be investigatedin detail. This study was initiated to investigate the effects of the a2-adrenergic receptor agonists clonidine and rilmenidineand the a2-adrenergic receptor antagonists yohimbine and efaroxan on spinal cholinergic receptors in the rat. Spinalmicrodialysis was used to measure in vivo changes of acetylcholine after administration of the ligands, with or withoutnicotinic receptor blockade. In addition, in vitro binding properties of the ligands on muscarinic and nicotinic receptorswere investigated. It was found that clonidine and rilmenidine increased, while yohimbine decreased spinal acetylcholinerelease. Efaroxan affected acetylcholine release differently depending on concentration. Nicotinic receptor blockade atten-uated the effect of all ligands. All ligands showed poor binding affinity for muscarinic receptors. On the other hand, allligands possessed affinity for nicotinic receptors. Clonidine and yohimbine binding was best fit to a one site binding curveand rilmenidine and efaroxan to a two site binding curve. The present study demonstrates that the tested a2-adrenergicreceptor ligands affect intraspinal acetylcholine release in the rat evoked by nicotinic receptor mechanisms in vivo, andthat they possess binding affinity to nicotinic receptors in vitro. The binding of a2-adrenergic receptor ligands to nicotinicreceptors might affect the intraspinal release of acetylcholine.

  • 19.
    Abelson, Klas
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Neuroscience.
    Kommalage, Mahinda
    Höglund, Urban
    Spinal cholinergic involvement after treatment with aspirin and paracetamol in rats2004In: Neurosci. Lett., ISSN 0304-3940, Vol. 368, no 1, 116-120 p.Article in journal (Refereed)
  • 20.
    Abelson, Klas
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Neuroscience, Comparative Medicine.
    Kommalage, Mahinda
    Höglund, Urban
    Spinal cholinergic involvement after treatment with aspirin and paracetamol in rats2004In: Neuroscience Letters, ISSN 0304-3940, Vol. 368, no 1, 116-120 p.Article in journal (Refereed)
  • 21.
    Abelson, Klas
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Neuroscience. Försöksdjursvetenskap.
    Röstlinger Goldkuhl, Renée
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Neuroscience. Försöksdjursvetenskap.
    Nylund, Anders
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Neuroscience. Försöksdjursvetenskap.
    Höglund, Urban
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Neuroscience. Försöksdjursvetenskap.
    The effect of ketamine on intraspinal acetylcholine release: Involvement of spinal nicotinic receptors2006In: Eur J Pharmacol, Vol. 534, 122-128 p.Article in journal (Refereed)
  • 22.
    Abelson, Klas S. P.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Comparative Medicine.
    Fard, Shahrzad Shirazi
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Comparative Medicine.
    Nyman, Julia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Comparative Medicine.
    Goldkuhl, Renée
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Comparative Medicine.
    Hau, Jann
    Distribution of [3H]-corticosterone in urine, feces and blood of male Sprague-Dawley rats after tail vein and jugular vein injections2009In: In Vivo, ISSN 0258-851X, E-ISSN 1791-7549, Vol. 23, no 3, 381-386 p.Article in journal (Refereed)
    Abstract [en]

    The present study aimed to investigate the time-course and distribution of [(3)H]-corticosterone in urine, feces and blood of male Sprague-Dawley rats after intravenous administration of a low dose (1 microCi), and to investigate whether different intravenous routes of administration may affect the dynamics of excreted [(3)H]-corticosterone in the feces. One microCi [(3)H]-corticosterone was injected intravenously either through the tail vein in manually restrained rats or through a jugular vein catheter three days after surgical implantation. Urine and feces were collected at different time points over 78 h from the rats injected in the tail vein, and blood and feces were collected over 48 h from rats injected in the jugular vein. In the blood, radioactivity peaked immediately and decreased rapidly within 90 minutes. The radioactivity was excreted in urine within six h and in feces after at least 12 h. Sixty percent of the radioactivity was detected in the urine and 40% in feces during the study period of 78 h. The detected amount of radioactivity in feces was higher and displayed a more pronounced peak 12 h after injection when the substance was administered through a jugular vein catheter compared to tail vein injection. The data obtained in the present study may serve as an important benchmark when choosing time points for fecal collection for quantification of corticosterone or corticosterone metabolites as a non-invasive measure of preceding HPA-axis activation.

  • 23. Abelson, Klas S. P.
    et al.
    Jacobsen, Kirsten R.
    Sundbom, Renée
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Comparative Medicine.
    Kalliokoski, Otto
    Hau, Jann
    Voluntary ingestion of nut paste for administration of buprenorphine in rats and mice2012In: Laboratory Animals. Journal of the Laboratory Animal Science Association, ISSN 0023-6772, E-ISSN 1758-1117, Vol. 46, no 4, 349-351 p.Article in journal (Refereed)
    Abstract [en]

    An adequate analgesic strategy is important to improve the postoperative recovery and welfare of laboratory rats and mice. It is desirable that the method for administering the drug is non-invasive and stress-free. We have previously validated a method for administering buprenorphine in a nut paste for voluntary ingestion. This method has many advantages over parenteral administration. To use the method in a successful way, however, it is important to prepare and administer the mix correctly. The present paper describes in detail how to implement the method, by means of habituation, presentation, adequate concentrations and amounts of buprenorphine/nut paste, and dosage of buprenorphine to rats and mice.

  • 24.
    Aberg, AC
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Lindmark, B
    Department of Neuroscience.
    Lithell, H
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Development and reliability of the General Motor Function Assessment Scale(GMF)-A performance-based measure of function-related dependence, pain andinsecurity.2003In: Disabil Rehabil, Vol. 25, 11- p.Article in journal (Refereed)
  • 25.
    Aberg, AC
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Lindmark, B
    Department of Neuroscience.
    Lithell, H
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Evaluation and application of the General Motor Function assessment scalein geriatric rehabilitation.2003In: Disabil Rehabil, Vol. 25, 9- p.Article in journal (Refereed)
  • 26.
    Aberg, Fredrik
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Neuroscience.
    Kozlova, Elena N
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Neuroscience.
    Metastasis-associated Mts1 (S100A4) protein in the developing and adult central nervous system2000In: J Comp Neurology, Vol. 424, 269- p.Article in journal (Refereed)
  • 27. Aberg-Wistedt, A
    et al.
    Agren, H
    Ekselius, Lisa
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Neuroscience.
    Bengtsson, F
    Akerblad, AC
    Sertraline vs Paroxetine in major depression: Clinical outcome after6 months of continuation therapy.2000In: J Clin Psychopharmacol. , Vol. 20, 645- p.Article in journal (Refereed)
  • 28.
    Abrahamsson, Eva
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Logopedi.
    Quick, Linnéa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Logopedi.
    Datorbaserad fonologisk lästräning för barn med hörselnedsättning: En undersökning av fonologisk medvetenhet och ordavkodning2015Independent thesis Advanced level (degree of Master (One Year)), 20 credits / 30 HE creditsStudent thesis
    Abstract [sv]

    Randomized controlled trials evaluating the effect of various forms of literacy training with reliable tests are lacking in Sweden today. The aim of the present study was to investigate whether a cross-over design and the use of phonologically matched wordlists specifically designed to detect transfer, would yield a more thorough method and reliable results. Six children with hearing impairment using hearing aids between 7 and 9 years of age took part in the study. The schools in which the children had their education were randomized into either an intervention group that started to practice phonics by means of a computer-assisted program after the first testing, or a control group that, continued as usual in school. Children were informed to practice daily with the program during four weeks in school. Children were tested with a battery of tests for phonological awareness, letter knowledge and word decoding at three occasions separated by four weeks. Results showed that the wordlists seemed reliable in establishing children’s decoding strategies as well as how word length affected reading speed. Both children who took part in the intervention and the control group improved their scores at the second testing. Thus, the computer-assisted reading intervention did not prove to be more effective than usual school activities. Due to a small number of participants, a large heterogeneity of the group and insufficient practice time, effects were difficult to detect. The present investigation should be considered a pilot study towards the use of more careful testing methods with adapted wordlists that enables the detection of transfer. But, to accomplish this, it is crucial to use a larger number of participants.

    Randomiserade kontrollerade studier som utvärderar effekten av olika former av läs- och skrivträning med tillförlitliga tester saknas i Sverige idag. Syftet med denna undersökning var att genomföra en interventionsstudie med cross-over design och använda fonologiskt matchade ordlistor specifikt utformade för att upptäcka transfer, för att ge utdelning för en mer grundlig metod och reliabla resultat. Sex barn mellan 7 och 9 års ålder som använde hörapparat deltog i studien. Skolorna som barnen gick i randomiserades till att antingen utgöra en interventionsgrupp, som började träna med ett ljudbaserat lästräningsprogram via dator efter första testningen, eller kontrollgrupp som fortsatte med vanlig skolundervisning. Barnen informerades att träna med programmet under fyra veckor dagligen i skolan. Barnen utförde ett testbatteri innehållande tester för fonologisk medvetenhet, bokstavskännedom och ordavkodning vid tre tillfällen med fyra veckors mellanrum. Resultaten visade att ordlistorna på ett reliabelt sätt kunde fastställa barns avkodningsstrategier samt hur ordlängd påverkade läshastigheten. Både interventions- och kontrollgruppen påvisade förbättring vid andra testningen. Dock kunde det inte påvisas att den datorbaserade lästräningen var mer effektiv än sedvanlig skolundervisning. Då deltagarantalet var litet, spridningen stor och träningstiden vid datorn var låg kan detta ha bidragit till att effekterna uteblev. Studien bör ses som en pilotstudie som går mot en noggrannare form av testmetod där användandet av anpassade ordlistor möjliggör upptäckt av transfer. För att åstadkomma detta är det emellertid avgörande att det ingår ett större deltagarantal.

  • 29. Abrahamsson, Hasse
    et al.
    Ostlund-Lindqvist, Ann-Margret
    Nilsson, Ralf
    Simren, Magnus
    Gillberg, Per-Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Pharmacology.
    Altered bile acid metabolism in patients with constipation-predominant irritable bowel syndrome and functional constipation2008In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 43, no 12, 1483-1488 p.Article in journal (Refereed)
    Abstract [en]

    Objective. Bile acids are derived from cholesterol and are potent physiological laxatives. The aim of this study was to investigate whether bile acid synthesis is altered in constipation. Material and methods. Female patients with constipation (23 IBS-C, 4 functional constipation (FC)) were studied and compared with non-constipated subjects (16 IBS-D, 20 healthy women). Body mass index (BMI), blood lipids, lanosterol, sitosterol, colonic transit (oro-anal transit time (OATT), reference=4.3 days) and stool frequency were measured. C4 (7--hydroxy-4-cholesten-3-one) levels reflecting bile acid synthesis were measured at 0800 h and 1300 h. Results. When all the groups of constipated and non-constipated subjects were compared, it was found that only stool frequency and OATT differed between groups (p 0.001). When constipated patients were categorized according to OATT, absence of the usual C4 increase at lunchtime was noted in 82% of patients with delayed OATT compared with 17% in subjects with normal OATT (p 0.001). Symptom severity did not differ between groups. A subset of the patients with severely delayed OATT had markedly elevated C4 levels. Conclusions. Patients with IBS-C and FC have marked changes in bile acid synthesis in relation to colonic transit. The diurnal rhythm is altered in the slow transit colon when there is no C4 peak at lunchtime. Alterations in bile acid metabolism may be implicated in the pathophysiology of constipation.

  • 30.
    Abrahamsson, Lotta
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Neuroscience, Logopedi.
    Ljung, Ida-Karin
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Neuroscience, Logopedi.
    Bliss i interaktion: - En samtalsanalytisk fallstudie av hur blissanvändare och tolkare tillsammans bygger upp yttranden2008Independent thesis Advanced level (degree of Master (One Year)), 20 credits / 30 HE creditsStudent thesis
  • 31.
    Abu Hamdeh, Sami
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Lytsy, Birgitta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology and Infectious Medicine, Clinical Bacteriology.
    Ronne-Engström, Elisabeth
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Surgical site infections in standard neurosurgery procedures-a study of incidence, impact and potential risk factors2014In: British Journal of Neurosurgery, ISSN 0268-8697, E-ISSN 1360-046X, Vol. 28, no 2, 270-275 p.Article in journal (Refereed)
    Abstract [en]

    Objectives. Surgical site infections (SSIs) may be devastating for the patient and they carry high economic costs. Studies of SSI after neurosurgery report an incidence of 1 - 11%. However, patient material, follow-up time and definition of SSI have varied. In the present study we prospectively recorded the prevalence of SSI 3 months after standard intracranial neurosurgical procedures. The incidence, impact and risk factors of SSI were analysed. Methods. We included patients admitted during 2010 to our unit for postoperative care after standard neurosurgical procedures. SSI was defined as evident with positive cultures from surgical samples or CSF, and/or purulent discharge during reoperation. Follow-up was done after 3 and 12 months and statistics was obtained after 3 months. The predictive values on the outcome of demographic and clinical factors describing the surgical procedure were evaluated using linear regression. Results. A total of 448 patients were included in the study and underwent a total of 466 procedures. Within 3 and 12 months, 33 and 88 patients, respectively, had died. Of the surviving patients, 20 (4.3% of procedures) developed infections within 3 months and another 3 (4.9% of procedures) within 12 months. Risk factors for SSI were meningioma, longer operation time, craniotomy, dural substitute, and staples in wound closure. Patients with SSI had significantly longer hospital stay. Multivariate analysis showed that factors found significant in univariate analysis frequently occur together. Discussion. We studied the prevalence of SSI after 3 and 12 months in a prospective 1-year material with standard neurosurgical procedures and found it to be 4.3% and 4.9%, respectively. The analysis of the results showed that a combination of parameters indicating a longer and more complicated procedure predicted the development of SSI. Our conclusion is that the prevention of SSI has to be done at many levels, especially with patients undergoing long surgical procedures.

  • 32.
    Abu Hamdeh, Sami
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Marklund, Niklas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Lannsjö, Marianne
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Rehabilitation Medicine. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Research and Development, Gävleborg.
    Howells, Tim
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Raininko, Raili
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Wikström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Enblad, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Extended anatomical grading in diffuse axonal injury using MRI: Hemorrhagic lesions in the substantia nigra and mesencephalic tegmentum indicate poor long-term outcome2017In: Journal of Neurotrauma, ISSN 0897-7151, E-ISSN 1557-9042, Vol. 5, no 34, 341-352 p.Article in journal (Refereed)
    Abstract [en]

    Clinical outcome after traumatic diffuse axonal injury (DAI) is difficult to predict. In this study, three magnetic resonance imaging (MRI) sequences were used to quantify the anatomical distribution of lesions, to grade DAI according to the Adams grading system, and to evaluate the value of lesion localization in combination with clinical prognostic factors to improve outcome prediction. Thirty patients (mean 31.2 years ±14.3 standard deviation) with severe DAI (Glasgow Motor Score [GMS] <6) examined with MRI within 1 week post-injury were included. Diffusion-weighted (DW), T2*-weighted gradient echo and susceptibility-weighted (SWI) sequences were used. Extended Glasgow outcome score was assessed after 6 months. Number of DW lesions in the thalamus, basal ganglia, and internal capsule and number of SWI lesions in the mesencephalon correlated significantly with outcome in univariate analysis. Age, GMS at admission, GMS at discharge, and low proportion of good monitoring time with cerebral perfusion pressure <60 mm Hg correlated significantly with outcome in univariate analysis. Multivariate analysis revealed an independent relation with poor outcome for age (p = 0.005) and lesions in the mesencephalic region corresponding to substantia nigra and tegmentum on SWI (p  = 0.008). We conclude that higher age and lesions in substantia nigra and mesencephalic tegmentum indicate poor long-term outcome in DAI. We propose an extended MRI classification system based on four stages (stage I—hemispheric lesions, stage II—corpus callosum lesions, stage III—brainstem lesions, and stage IV—substantia nigra or mesencephalic tegmentum lesions); all are subdivided by age (≥/<30 years).

  • 33.
    Abu Hamdeh, Sami
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Marklund, Niklas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Lannsjö, Marianne
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Rehabilitation Medicine.
    Howells, Tim
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Raininko, Raili
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Wikström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Enblad, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    MRI analysis of diffuse axonal injury - Hemorrhagic lesions in the mesencephalon idicate poor long-term outcome2016In: MRI analysis of diffuse axonal injury - Hemorrhagic lesions in the mesencephalon idicate poor long-term outcome, Springer, 2016, Vol. 7, Suppl. 1, B-0814Conference paper (Refereed)
    Abstract [en]

    Purpose: Clinical outcome after traumatic diffuse axonal injury (DAI) is difficult to predict. Three MRI techniques were compared in demonstrating acute brain lesions.  Relationship of the anatomical distribution of the lesions in combination with clinical prognostic factors to outcome after 6 months was evaluated.  

    Methods and Materials: Thirty patients, aged 16-60 years (mean 31.2 years) with severe DAI (Glasgow Motor Score = GMS < 6) were examined with MRI at 1.5T within one week after the injury. A diffusion-weighted (DW) sequence (SE-EPI, b value 1000 s/mm2), a T2*-weighted gradient echo (T2*GRE) sequence and a susceptibility-weighted (SWI) sequence were evaluated by two independent reviewers with short and long neuroradiological experiences. Clinical outcome was assessed with Extended Glasgow Outcome Score (GOSE) after ≥ 6 months.

    Results: Interreviewer agreement for DAI classification was very good (ҡ 0.82 – 0.91) with all three sequences. SWI visualized more lesions than the T2*GRE or DW sequence.  In univariate analysis, number of DW lesions in the deep gray matter area including the internal capsules, number of SWI lesions in the mesencephalon, age, and GMS at admission and discharge correlated significantly with poor outcome.  Multivariate analysis only revealed an independent relation with poor outcome for age (p = 0.011) and lesions in the mesencephalic region including crura cerebri, substantia nigra and tegmentum on SWI (p = 0.032).

    Conclusion: SWI is the most sensitive technique to visualize lesions in DAI. Age over 30 years and hemorrhagic mesencephalic lesions anterior to the tectum are indicators of poor long-term outcome in DAI.

  • 34. Adam, GIR
    et al.
    Reneland, R
    Andersson, M
    Risinger, C
    Nilsson, M
    Lewander, T
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Neuroscience.
    Pharmacogenomics to predict drug response2000In: Pharmacogenomics, Vol. 1Article in journal (Refereed)
  • 35.
    Addo, Rebecka N.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience. Stockholm Univ, Dept Psychol, Gosta Ekman Lab, Frescati Hagvag 9A, S-10691 Stockholm, Sweden..
    Wiens, Stefan
    Stockholm Univ, Dept Psychol, Gosta Ekman Lab, Frescati Hagvag 9A, S-10691 Stockholm, Sweden..
    Nord, Marie
    Stockholm Univ, Dept Psychol, Gosta Ekman Lab, Frescati Hagvag 9A, S-10691 Stockholm, Sweden..
    Larsson, Maria
    Stockholm Univ, Dept Psychol, Gosta Ekman Lab, Frescati Hagvag 9A, S-10691 Stockholm, Sweden..
    Olfactory Functions in Adults With Autism Spectrum Disorders2017In: Perception, ISSN 0301-0066, E-ISSN 1468-4233, Vol. 46, no 3-4, 530-537 p.Article in journal (Refereed)
    Abstract [en]

    Autism spectrum disorders (ASD) are often characterized by atypical sensory behavior (hyperor hyporeactivity) although evidence is scarce regarding olfactory abilities in ASD; 16 adults with high-functioning ASD (mean age: 38.2, SD: 9.7) and 14 healthy control subjects (mean age: 42.0 years, SD: 12.5) were assessed in odor threshold, free and cued odor identification, and perceived pleasantness, intensity, and edibility of everyday odors. Although results showed no differences between groups, the Bayes Factors (close to 1) suggested that the evidence for no group differences on the threshold and identification tests was inconclusive. In contrast, there was some evidence for no group differences on perceived edibility (BF01 = 2.69) and perceived intensity (BF01 = 2.80). These results do not provide conclusive evidence for or against differences between ASD and healthy controls on olfactory abilities. However, they suggest that there are no apparent group differences in subjective ratings of odors.

  • 36.
    Adelsköld, Signe
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Physiotheraphy.
    Thalin, Hanna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Physiotheraphy.
    Reliabilitets- och validitetsprövning av Modifierad Self-efficacy Scale för patienter med långvarig smärta2010Independent thesis Basic level (professional degree), 10 credits / 15 HE creditsStudent thesis
    Abstract [sv]

    Syfte: Studiens syfte var att reliabilitetspröva stabiliteten för M-SES för patienter med långvarig smärta genom test-retest metoden. Syftet var även att undersöka samtidig validitet för M-SES, genom att utföra M-SES och SES mätt vid samma tillfälle.

    Metod: I studien undersöktes self-efficacy instrumentet M-SES på Uppsala Akademiska sjukhus, på avdelningarna för Smärtcentrum och Smärtrehabilitering. Frågeställningarna berörde vilken stabilitets reliabilitet mätt med test-retest som förelåg hos M-SES, samt vilken grad av samtidig validitet som förelåg för M-SES korrelerat med SES. Den slutliga undersökningsgruppen bestod i frågeställningen om stabilitets reliabilitet av 29 patienter (23 kvinnor, sex män), och i frågeställning om samtidig validitet av 22 patienter (17 kvinnor, fem män).

    Resultat: Vid prövning av stabilitets reliabilitet för M-SES visade resultatet en stark korrelation, med korrelationskoefficient 0,92 och p<0,05. Det förelåg även en god överrensstämmelse för test-retest undersökningen. Prövningen av samtidig validitet för M-SES visade en stark korrelation, med koefficienten 0,88 och p<0,05.

    Konklusion: Studiens resultat visade att det förelåg en stark stabilitets reliabilitet och samtidig validitet för M-SES för patienter med långvarig smärta. Då studien genomfördes med få deltagare bör resultatet tolkas med försiktighet.

  • 37.
    Adencreutz, M
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Neuroscience. Försöksdjursvetenskap.
    Hau, Jann
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Neuroscience. Försöksdjursvetenskap.
    Studies of neonatal and juvenile neuromuscular locomotor development of C57BL/6/Bkl, 129SvEv/Bkl and F1 hybrid mice in swim tests2004In: In vivo, Vol. 18, no 6, 733-737 p.Article in journal (Refereed)
  • 38. Adler, Hans
    et al.
    Frisk, Max
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Neuroscience.
    Lidberg, Lars
    Severe delinquency in young people: Background factors and characterizing features1995In: Nordic Journal of Psychiatry, Vol. 49, 263- p.Article in journal (Refereed)
  • 39.
    af Klinteberg, B
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Neuroscience.
    Antisocialitet ur ett neuropsykologiskt perspektiv.2002In: In W Rundwuist & K Carpelan-Söderholm (Eds), Ung med tung social problematik. Hur kan vi förstå, förutsäga och planera för framtida behandling?, Stockholm: Statens institutionsstyrelse. , 2002, 49- p.Chapter in book (Other scientific)
  • 40.
    af Klinteberg, B
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Neuroscience.
    Psychobiological patterns at adult age: relationships to personality and early behavior. 2000In: In LR Bergman, R Cairns, L-G Nilsson & L Nystedt (Eds), Developmental Science and the Holistic Approach, New York: Erlbaum , 2000, 209- p.Chapter in book (Other scientific)
  • 41.
    af Klinteberg, B
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Neuroscience.
    Tidiga problembeteende. Personlighetsaspekter, rökning, alkohol och kriminalitet.2002In: In S Andréasson (Ed), Den svenska supen i det nya Europa. Nya villkor för alkoholprevention: en kunskapsöversikt., Stockholm: Statens Folkhälsoinsitut , 2002, Vol. 11, 95- p.Chapter in book (Other scientific)
  • 42.
    af Klinteberg, B
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Neuroscience.
    Underlying vulnerability influencing outcome factors/behaviors in psychosocial disturbances.2002In: In RR Corrado, R Roesch, SD Hart & JK Gierowski (Eds), Multiproblem violent youth: a foundation for comparative research on needs, interventions and outcomes., Amsterdam: IOS Press , 2002Chapter in book (Other scientific)
  • 43. Af Klinteberg, B
    et al.
    Oreland, L
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Neuroscience.
    Hyperactive and aggressive behaviors in childhood as related to low platelet monoamine oxidase (MAO) activity at adults age: A longitudinal study of male subjects1995In: Personal Indiv Diff, Vol. 19, 373- p.Article in journal (Refereed)
  • 44. af Klinteberg, Britt
    et al.
    Alm, Per-Olof
    Oreland, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Pharmacology.
    Serotonin, personality and smoking2000Conference paper (Refereed)
  • 45.
    af Klinteberg, Britt
    et al.
    Stockholm Univ, Dept Psychol, Stockholm, Sweden.;Stockholm Univ, Karolinska Inst, Ctr Hlth Equ Studies, Sveav 160, SE-10691 Stockholm, Sweden.;Karolinska Inst, Dept Womens & Childrens Hlth, Stockholm, Sweden..
    Johansson, Sven -Erik
    Karolinska Inst, Ctr Family & Community Med, Stockholm, Sweden..
    Levander, Maria
    Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden..
    Alm, Per Olof
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Oreland, L
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Smoking habits - Associations with personality/behavior, platelet monoamine oxidase activity and plasma thyroid hormone levels2017In: Personality and Individual Differences, ISSN 0191-8869, E-ISSN 1873-3549, Vol. 118, 71-76 p.Article in journal (Refereed)
    Abstract [en]

    The objective was to outline results from our scientific studies on the associations among childhood behavior, adult personality, and biochemical factors in smoking habits. The studies consisted of: (1) follow-up of young criminals and controls, subdivided into risk for antisocial behavior groups, based on childhood rating levels of a projective test; and adult smoking habit groups; and (2) a large group of young adults examined on the same inventories. Personality in terms of KSP and EPQ-I scale scores, controlled for intelligence, indicated that the high and very high risk groups displayed significantly higher self-rated impulsiveness, anxiety, and nonconformity, as compared to the low risk group. Further, the very high risk group subjects, found to be overrepresented among subjects with heavy smoking habits, displayed lower mean platelet MAO-B activity and higher thyroid hormone levels than the low risk group. Thus, the higher the childhood risk for antisocial behavior, the clearer the adult personality pattern making subjects more disposed for smoking appeared; and the higher smoking habits, the stronger the relationships with biochemical measures. Results are discussed in terms of possible underlying mechanisms influencing personality and smoking habits. 

  • 46.
    af Klinteberg, Britt
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Neuroscience. psykiatri UAS.
    Lang, S
    Freidenfelt, J
    Alm, P-O
    Risk indicators and stress situations as related to pursuant disinhibitory psychosocial disturbances.2004In: Personality and extreme stress, Warsaw: Gdansk Psychology Publishing , 2004, 83-99 p.Chapter in book (Other (popular scientific, debate etc.))
  • 47.
    af Klinteberg, Britt
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Neuroscience. Farmakologi 1.
    von Knorring, Lars
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Neuroscience. Psykiatri UAS.
    Oreland, Lars
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Neuroscience. Farmakologi 1.
    On the psychobiology of impulsivity2004In: On the psychobiology of personality: Essays in honor of Marvin Zuckerman, Elsevier B.V., Amsterdam , 2004, 455-478 p.Chapter in book (Refereed)
  • 48.
    Ager, Emma
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Logopedi.
    Solli, Elin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Logopedi.
    The PhonicStick: A Swedish Study: How do children age 5 and 6 handle the PhonicStick and will the use of it affect their phonological awareness?2009Independent thesis Advanced level (degree of Master (One Year)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    Phonological awareness is the ability to recognise, identify and manipulate components in words. Phonological awareness is an important part of the early literacy learning, although researchers disagree on how the connection arises. In the United Kingdom, synthetic phonics is a recommended way to teach literacy and the Jolly Phonics is a common approach within this method. In Sweden, mostly synthetic but also analytic methods are used for literacy teaching. The PhonicStick is developed as a communication device for impaired people and is based on the Jolly Phonics. In this study, the PhonicStick was being tested on children aged 5 and 6 years in mainstream pre-school classes to evaluate the use of it and its use for improvement of phonological awareness. The participating children were randomly divided into a test and a control group. All children were pre- and post-tested to analyse the possible improvement of parts of the phonological awareness. The test group went through three PhonicStick sessions, including different games and tests. The results from the pre- and post-tests of phonological awareness showed no significant differences between the test and control group. However, four out of five PhonicStick tests showed a significant improvement between session 1 and session 3. This shows that the children in the study were able to handle the PhonicStick after only three sessions, including remembering phonics the without visual information and producing words including two or three phonics.

  • 49.
    Aggarwal, Tanya
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Hoeber, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Regenerative neurobiology.
    Ivert, Patrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Regenerative neurobiology.
    Vasylovska, Svitlana
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Regenerative neurobiology.
    Kozlova, Elena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Regenerative neurobiology.
    Boundary Cap Neural Crest Stem Cells Promote Survival of Mutant SOD1 Motor Neurons.2017In: Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics, ISSN 1878-7479, Vol. 14, no 3, 773-783 p.Article in journal (Refereed)
    Abstract [en]

    ALS is a devastating disease resulting in degeneration of motor neurons (MNs) in the brain and spinal cord. The survival of MNs strongly depends on surrounding glial cells and neurotrophic support from muscles. We previously demonstrated that boundary cap neural crest stem cells (bNCSCs) can give rise to neurons and glial cells in vitro and in vivo and have multiple beneficial effects on co-cultured and co-implanted cells, including neural cells. In this paper, we investigate if bNCSCs may improve survival of MNs harboring a mutant form of human SOD1 (SOD1(G93A)) in vitro under normal conditions and oxidative stress and in vivo after implantation to the spinal cord. We found that survival of SOD1(G93A) MNs in vitro was increased in the presence of bNCSCs under normal conditions as well as under oxidative stress. In addition, when SOD1(G93A) MN precursors were implanted to the spinal cord of adult mice, their survival was increased when they were co-implanted with bNCSCs. These findings show that bNCSCs support survival of SOD1(G93A) MNs in normal conditions and under oxidative stress in vitro and improve their survival in vivo, suggesting that bNCSCs have a potential for the development of novel stem cell-based therapeutic approaches in ALS models.

  • 50. Agnafors, S.
    et al.
    Sydsjö, G.
    Comasco, Erika
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neuro-psycho-pharmacology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Bladh, M.
    Oreland, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neuro-psycho-pharmacology.
    Svedin, C.
    Behaviour problems in children-a longitudinal study of genetic and environmental factors2015In: European Child and Adolescent Psychiatry, ISSN 1018-8827, E-ISSN 1435-165X, Vol. 24, S35-S35 p.Article in journal (Other academic)
1234567 1 - 50 of 6436
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