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  • 51. Bröjer, Caroline
    et al.
    Järhult, Josef D
    Muradrasoli, Shaman
    Söderström, Hanna
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Olsen, Björn
    Gavier-Widén, Dolores
    Pathobiology and virus shedding of low-pathogenic avian influenza virus (a/h1n1) infection in mallards exposed to oseltamivir2013In: Journal of Wildlife Diseases, ISSN 0090-3558, E-ISSN 1943-3700, Vol. 49, no 1, p. 103-113Article in journal (Refereed)
    Abstract [en]

    Low-pathogenic avian influenza (LPAI) viruses in wild birds are important as they can constitute the basis for the development of highly pathogenic avian influenza viruses or form part of human-adapted strains with pandemic potential. However, the pathogenesis of LPAI viruses is not well characterized in dabbling ducks, one of the natural reservoirs of LPAI viruses. Between 21 September 2009 and 21 December 2009, we used real-time reverse transcriptase polymerase chain reaction (q-PCR), histopathology, and immunohistochemistry (IHC) to study Mallards (Anas platyrhynchos) infected with an influenza A/H1N1 virus isolated from a wild Mallard in Sweden. The ducks were either inoculated intraesophageally ("artificial infection") or infected by virus shed by other ducks in the experiment ("contact infection"). The ducks were subjected to three low concentrations (80 ng/L, 1 μg/L, and 80 μg/L) of the active metabolite of oseltamivir (Tamiflu(®)), oseltamivir carboxylate (OC), which resulted in the development of the viral resistance mutation H274Y at 1 and 80 μg/L. The LPAI virus infection was localized to the intestinal tract and cloacal bursa except in one Mallard. The exception was a duck euthanized 1 day postinoculation, whose infection was located solely in the lung, possibly due to intratracheal deposition of virus. The intestinal infection was characterized by occasional degenerating cells in the lamina propria and presence of viral antigen as detected by IHC, as well as positive q-PCR performed on samples from feces and intestinal contents. Histopathologic changes, IHC positivity, and viral shedding all indicated that the infection peaked early, around 2 days postinfection. Furthermore, more viral antigen and viral RNA were detected with IHC and q-PCR in the proximal parts early in the infection. There was no obvious difference in the course of the infection in artificial versus contact infection, when the level of OC was increased from 80 ng/L to 1 μg/L (based on IHC and q-PCR), when the level of OC was increased to 80 μg/L, or when the resistance mutation H274Y developed (based on q-PCR).

  • 52.
    Börjesson, Andreas
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Cell Biology.
    Investigations of Strategies to Counteract Proinflammatory Cytokines in Experimental Type 1 Diabetes2008Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Type 1 diabetes (T1D) is a chronic autoimmune disease targeted against the pancreatic β-cells. Proinflammatory cytokines are considered to play a major role in the destruction of the insulin-producing β-cells. This thesis studied strategies to counteract proinflammatory cytokines in experimental T1D. Both animal models for T1D as well as β-cell preparations exposed in vitro to putative noxious conditions were examined.

    In the first study we observed that cytokine treatment of mouse pancreatic islets lacking inducible nitric oxide synthase (iNOS) induced a prolongation of the early stimulatory phase of glucose stimulated insulin secretion. Various experiments led to the conclusion that this prolonged stimulatory effect may involve the DAG/PLD/PKC pathway.

    Next, we transplanted mouse islets deficient in iNOS to spontaneously diabetic NOD mice. We observed a normalization of hyperglycemia but not a delayed allograft rejection compared to transplanted wild type islets. Thus, absence of iNOS in the graft was not sufficient to prolong allograft survival.

    In paper III we found that sustained glucose stimulation of rat pancreatic islets was coupled to a decreased conversion of proinsulin to insulin. Islet treatment with IL-1β was also coupled to a decreased proinsulin conversion. Islet proconvertase activity may be a target in islet damage.

    In paper IV prolactin (PRL) was administered to mice in the multiple low dose streptozotocin model and we observed that PRL enhanced a Th2 response. This may contribute to the protective action by PRL in this model of autoimmune T1D.

    Finally, by examining β-cells overexpressing Suppressor of cytokine signalling 3 (SOCS-3) it was found that this could inhibit IL-1β induced signalling through the NF-κB and MAPK pathways. SOCS-3 overexpression also inhibited apoptosis induced by cytokines in primary β-cells. Lastly, we demonstrated that SOCS-3 transgenic islets were protected in an allogeneic transplantation model.

  • 53.
    Böttiger, Anna
    Örebro University, School of Health and Medical Sciences.
    Genetic variation in the folate receptor-alpha and methylenetetrahydrofolate reductase genes as determinants of plasma homocysteine concentrations2008Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Elevated total plasma homocysteine (tHcy) is a risk factor for cardiovascular disease and neurocognitive disease such as dementia. The B vitamins folate and B12 are the main de terminants of tHcy. tHcy concentration can also be affected by mutations in genes coding for receptors, enzymes and transporters important in the metabolism of Hcy. This thesis focuses on mutations in the genes for folate receptor-alpha and methylenetetrahydrofolate reductase (MTHFR) and the effect they have on tHcy concentrations.

    Six novel mutations in the gene for folate receptor-alpha were described in Paper I. Taken together they exist in a population with a prevalence of approximately 1% and thus are not unusual. There may be an association of –69dupA and –18C>T to tHcy but for the 25-bp deletion, –856C>T, –921T>C and –1043G>A there is probably no association to tHcy. Mutation screening was continued and four additional mutations, 1314G>A, 1816delC, 1841G>A and 1928C>T, were described in Paper II. The prevalences for the heterozygotes were between 0.5% and 13% in an elderly population. There was no significant difference in prevalence between the elderly subjects and patients with dementia. The 1816(–)-allele and the 1841A-allele were in complete linkage and the haplotype 1816(–)-1841A may possibly have a tHcy raising effect. The 1314G>A and 1928C>T mutations had no association to tHcy.

    The genotype prevalences and haplotype frequencies of the MTHFR 677C>T, 1298A>C and 1793G>A polymorphisms were determined in a population sample of Swedish children and adolescents (Paper III). The MTHFR 677T-allele was associated with increased tHcy concentrations in both children and adolescents. A small elevating effect of the 1298C-allele and a small lowering effect of the 1793A-allele could be shown. In an epidemiological sample of adults from the Canary Islands, Spain, data for serum folate and vitamin B12 were used for a broader study of the nutrigenetic impact on tHcy (Paper IV). The 677T-allele had a significant tHcy increasing effect in men but not in women. The 1298C-allele had a minor elevating effect on tHcy in men with the 677CT genotype. It was not possible to document any effect of the 1793A-allele on tHcy due to its low prevalence. A slightly superior explanatory power for the genetic impact was obtained using the MTHFR haplotypes in the analysis compared to the MTHFR 677C>T genotype-based approach in both the Swedish children and adolescents and in the Spanish adults. Therefore MTHFR haplotypes should be considered when analysing the impact of the MTHFR 677C>T, 1298A>C and 1793G>A polymorphisms on tHcy.

    Notwithstanding the large geographical distance between our study populations the haplotype composition is quite similar. The MTHFR 677T-allele is slightly more prevalent in Spain compared to Sweden but it has only an effect on tHcy in the Spanish men. Age, gender and factors linked to the ethnicity of the studied subjects, seem to be able to override the nutrigenetic impact of tHcy-raising genotypes or haplotypes in particular settings, such as in the Spanish women in our study. Gene-nutrient interactions on plasma tHcy levels thus may or may not exist in a certain population. The transferability of nutrigenetic findings may therefore be limited, and must be re-evaluated for each particular setting of age-gender-ethnicity.

  • 54.
    Cancar, Anja
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Serbia’s way to accession with the European Union and the European Medicines Agency: a comparison of regulatory activity in the field of pharmaceuticals in Serbia and Sweden2014Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    Introduction:  On 24 January, 2014 Serbia was approved opening negotiations on accession into the European Union (EU). The European Commission is responsible for launching assistance programmes to support preparatory procedures for the candidate countries; one of those programmes is the Instrument for pre-accession Assistance (IPA) programme. The aim of the IPA programme is to build contacts and relationships between the European Medicines Agency (EMA) and Serbia’s Medicines and Medical Devices Agency (ALIMS), for future collaboration in the EMA activities and its relationship with the Member States of EU.

    Aim: The aim is to describe regulatory activities of ALIMS on human medicines, since the country is not yet a Member State of the EU and to put this into relation with Sweden, a Member State of the EU, which may promote new activities to be introduced in ALIMS’s regulatory work.

    Method: This is a descriptive comparative literature report of institutions working with pharmaceutical regulatory activities.

    Findings: The Serbian Law on Medicines and Medical Devices, established in 2010 suggests that the activities of ALIMS are generally in accordance with the EU standards and guidelines. Since Serbia is not yet a member of the EU, the pharmaceutical regulatory system for granting centralized authorization or marketing authorization based on mutual recognition is not yet possible. However, the Law of Medicines and Medical Devices states that exceptions can be made and ALIMS can issue authorization of centrally authorized medicines if it has reasons related to protection of public health.

    Conclusions: ALIMS has a well developed regulatory authority thanks to international collaboration and a desire to become an EU Member State. 

  • 55.
    Carlsson, Hans-Erik
    et al.
    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.
    Faheem, Shaik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Comparative Medicine.
    Tufvesson, Måns
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Comparative Medicine.
    Hau, Jann
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Comparative Medicine.
    Separation of pair housed roosters is associated with transient increased fecal corticosterone excretion2009In: Research in Veterinary Science, ISSN 0034-5288, E-ISSN 1532-2661, Vol. 86, no 1, p. 183-187Article in journal (Refereed)
    Abstract [en]

    Immunoreactive corticosterone and corticosterone metabolites (ICCM) were quantified in excreta of permanently single housed (n=10) and permanently pair housed (n=20) roosters. The pair housed roosters were separated and single housed, and ICCM were quantified in the droppings before and during 15 days after separation. There was no statistically significant difference in ICCM excretion in the droppings between the permanently single or pair housed roosters. After separation, however, the previously pair housed roosters showed a significantly transient elevated excretion of ICCM in droppings the second day after separation indicating that the separation and relocation is associated with an activation of the hypothalamic-pituitary-adrenal axis. The excretion of ICCM in droppings was not correlated to the concentration of ICCM in droppings. It is thus important that excretion of ICCM be expressed as amount excreted per time unit since the total excretion is dependant on both concentration of ICCM and amount of droppings produced.

  • 56.
    Cederquist, Kristina
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences.
    Palmqvist, Richard
    Emanuelsson, Monica
    Golovleva, Irina
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Medical and Clinical Genetics.
    Grönberg, Henrik
    Retained immunohistochemical staining in a large Swedish HNPCC family with a pathogenic MLH1 missense mutationManuscript (preprint) (Other academic)
  • 57.
    Chee-Sanford, Joanne C.
    et al.
    U.S. Department of Agriculture , Agricultural Research Service, Urbana, IL, USA.
    Krapac, Ivan J.
    Illinois State Geological Survey, Champaign, IL, USA.
    Yannarell, Anthony C.
    University of Illinois at Urbana-Champaign.
    Mackie, Roderick I.
    University of Illinois at Urbana-Champaign.
    29. Environmental Impacts of Antibiotic Use in the Animal Production Industry2012In: Ecology and Animal Health / [ed] Leif Norrgren and Jeffrey Levengood, Uppsala: Baltic University Press , 2012, 2, p. 228-239Chapter in book (Other (popular science, discussion, etc.))
  • 58. Cif, Laura
    et al.
    Hariz, Marwan
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience. Unit of Functional Neurosurgery, University College London-Institute of Neurology, Queen Square, London, UK.
    Seventy Years of Pallidotomy for Movement Disorders2017In: Movement Disorders, ISSN 0885-3185, E-ISSN 1531-8257, Vol. 32, no 7, p. 972-982Article in journal (Other academic)
    Abstract [en]

    The year 2017 marks the 70th anniversary of the birth of human stereotactic neurosurgery. The first procedure was a pallidotomy for Huntington's disease. However, it was for Parkinson's disease that pallidotomy was soon adopted worldwide. Pallidotomy was abandoned in the late 1950s in favor of thalamotomy because of the latter's more striking effect on tremor. The advent of levodopa put a halt to all surgery for PD. In the mid-1980s, Laitinen reintroduced the posteroventral pallidotomy of Leksell, and this procedure spread worldwide thanks to its efficacy on most parkinsonian symptoms including levodopa-induced dyskinesias and thanks to basic scientific work confirming the role of the globus pallidus internus in the pathophysiology of PD. With the advent of deep brain stimulation of the subthalamic nucleus, pallidotomy was again abandoned, and even DBS of the GPi has been overshadowed by STN DBS. The GPi reemerged in the late 1990s as a major stereotactic target for DBS in dystonia and, recently, in Tourette syndrome. Lately, lesioning of the GPI is being proposed to treat refractory status dystonicus or to treat DBS withdrawal syndrome in PD patients. Hence, the pallidum as a stereotactic target for either lesioning or DBS has been the phoenix of functional stereotactic neurosurgery, constantly abandoned and then rising again from its ashes. This review is a tribute to the pallidum on its 70th anniversary as a surgical target for movement disorders, analyzing its ebbs and flows and highlighting its merits, its versatility, and its resilience.

  • 59.
    Cooray, Ruby
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Waller, Karin Persson
    Venge, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Haptoglobin comprises about 10% of granule protein extracted from bovine granulocytes isolated from healthy cattle2007In: Veterinary Immunology and Immunopathology, ISSN 0165-2427, E-ISSN 1873-2534, Vol. 119, no 3-4, p. 310-315Article in journal (Refereed)
    Abstract [en]

    Haptoglobin (Hp) is a plasma protein with haemoglobin binding capacity important in maintaining the iron homeostasis and in disease processes influenced by iron metabolism. In cattle Hp is one of the major acute phase proteins, and increases rapidly during infectious disease. At acute clinical mastitis in dairy cows the Hp concentration increases markedly both in blood and milk. Hepatocytes are considered to be the main origin of Hp, but expression of Hp mRNA has also been found in the mammary gland and leukocytes in healthy cattle. In the present study we show that bovine granulocytes, isolated from peripheral blood of healthy cattle, contain abundant amounts of Hp within the granules. As shown by two-dimensional gel electrophoresis (2-DE) in combination with matrix assisted laser desorption ionization-time of flight-mass spectrometry (MALDI-ToF-MS) bovine granulocyte Hp consists of two sets of peptides ca. 20 kDa (a-chains) and ca. 40 kDa ((3-chains) with multiple iso-forms.

  • 60.
    Coronado, Liani
    et al.
    Centro Nacional de Sanidad Agropecuaria (CENSA), OIE Collaborating Centre for Diagnosis and Risk Analysis of the Caribbean Region, La Habana 32700, Cuba.
    Bohórquez, José Alejandro
    OIE Reference Laboratory for Classical Swine Fever, IRTA-CReSA, Campus de la Universitat Autònoma de Barcelona, 08193, Bellaterra, Spain.
    Muñoz-González, Sara
    OIE Reference Laboratory for Classical Swine Fever, IRTA-CReSA, Campus de la Universitat Autònoma de Barcelona, 08193, Bellaterra, Spain.
    Pérez, Lester Josue
    University of Illinois, College of Veterinary Science, Department of Clinical Veterinary Medicine, Urbana, Illinois, 61802, United States.
    Rosell, Rosa
    OIE Reference Laboratory for Classical Swine Fever, IRTA-CReSA, Campus de la Universitat Autònoma de Barcelona, 08193, Bellaterra, Spain.
    Fonseca Rodriguez, Osvaldo
    National Centre for Animal and Plant Health (CENSA), OIE Collaborating Centre for Disaster Risk Reduction in Animal Health, San José de las Lajas, Mayabeque, Cuba.
    Delgado, Laiyen
    National Centre for Animal and Plant Health (CENSA), OIE Collaborating Centre for Disaster Risk Reduction in Animal Health, San José de las Lajas, Mayabeque, Cuba.
    Perera, Carmen Laura
    Centro Nacional de Sanidad Agropecuaria (CENSA), OIE Collaborating Centre for Diagnosis and Risk Analysis of the Caribbean Region, La Habana 32700, Cuba.
    Frías, María Teresa
    Centro Nacional de Sanidad Agropecuaria (CENSA), OIE Collaborating Centre for Diagnosis and Risk Analysis of the Caribbean Region, La Habana 32700, Cuba.
    Ganges, Llilianne
    OIE Reference Laboratory for Classical Swine Fever, IRTA-CReSA, Campus de la Universitat Autònoma de Barcelona, 08193, Bellaterra, Spain.
    Investigation of chronic and persistent classical swine fever infections under field conditions and their impact on vaccine efficacy2019In: BMC Veterinary Research, ISSN 1746-6148, E-ISSN 1746-6148, Vol. 15, no 1, article id 247Article in journal (Refereed)
    Abstract [en]

    Background: Recent studies have hypothesized that circulation of classical swine fever virus (CSFV) variants when the immunity induced by the vaccine is not sterilizing might favour viral persistence. Likewise, in addition to congenital viral persistence, CSFV has also been proven to generate postnatal viral persistence. Under experimental conditions, postnatal persistently infected pigs were unable to elicit a specific immune response to a CSFV live attenuated vaccine via the mechanism known as superinfection exclusion (SIE). Here, we study whether subclinical forms of classical swine fever (CSF) may be present in a conventional farm in an endemic country and evaluate vaccine efficacy under these types of infections in field conditions.

    Results: Six litters born from CSF-vaccinated gilts were randomly chosen from a commercial Cuban farm at 33 days of age (weaning). At this time, the piglets were vaccinated with a lapinized live attenuated CSFV C-strain vaccine. Virological and immunological analyses were performed before and after vaccination. The piglets were clinically healthy at weaning; however, 82% were viraemic, and the rectal swabs in most of the remaining 18% were positive. Only five piglets from one litter showed a specific antibody response. The tonsils and rectal swabs of five sows were CSFV positive, and only one of the sows showed an antibody response. After vaccination, 98% of the piglets were unable to clear the virus and to seroconvert, and some of the piglets showed polyarthritis and wasting after 36 days post vaccination. The CSFV E2 glycoprotein sequences recovered from one pig per litter were the same. The amino acid positions 72(R), 20(L) and 195(N) of E2 were identified in silico as positions associated with adaptive advantage.

    Conclusions: Circulation of chronic and persistent CSF infections was demonstrated in field conditions under a vaccination programme. Persistent infection was predominant. Here, we provide evidence that, in field conditions, subclinical infections are not detected by clinical diagnosis and, despite being infected with CSFV, the animals are vaccinated, rather than diagnosed and eliminated. These animals are refractory to vaccination, likely due to the SIE phenomenon. Improvement of vaccination strategies and diagnosis of subclinical forms of CSF is imperative for CSF eradication.

  • 61.
    Coronado, Liani
    et al.
    Centro Nacional de Sanidad Agropecuaria (CENSA), OIE Collaborating Centre for Diagnosis and Risk Analysis of the Caribbean Region, La Habana 32700, Cuba.
    Rios, Liliam
    University of New Brunswick, Reiman Cancer Research Laboratory, Faculty of Medicine, Saint John, NB, E2L 4L5 Canada.
    Frías, María Teresa
    Centro Nacional de Sanidad Agropecuaria (CENSA), OIE Collaborating Centre for Diagnosis and Risk Analysis of the Caribbean Region, La Habana 32700, Cuba.
    Amarán, Laymara
    National Laboratory for Veterinary Diagnostic (NLVD), Avenida 51 No. 33 222, Arroyo Arenas, La Lisa, La Habana, Cuba.
    Naranjo, Paula
    Veterinary Medicine Institute, Havana, Cuba.
    Percedo, María Irian
    Centro Nacional de Sanidad Agropecuaria (CENSA), OIE Collaborating Centre for Diagnosis and Risk Analysis of the Caribbean Region, La Habana 32700, Cuba.
    Perera, Carmen Laura
    Centro Nacional de Sanidad Agropecuaria (CENSA), OIE Collaborating Centre for Diagnosis and Risk Analysis of the Caribbean Region, La Habana 32700, Cuba.
    Prieto, Felix
    National Laboratory for Veterinary Diagnostic (NLVD), Avenida 51 No. 33 222, Arroyo Arenas, La Lisa, La Habana, Cuba.
    Fonseca-Rodriguez, Osvaldo
    Umeå University, Faculty of Medicine, Department of Epidemiology and Global Health.
    Perez, Lester J
    University of Illinois, College of Veterinary Science, Department of Clinical Veterinary Medicine, Urbana, Illinois, 61802 United States.
    Positive selection pressure on E2 protein of classical swine fever virus drives variations in virulence, pathogenesis and antigenicity: implication for epidemiological surveillance in endemic areas: Variability of positive selected strain of classical swine fever virus2019In: Transboundary and Emerging Diseases, ISSN 1865-1674, E-ISSN 1865-1682Article in journal (Refereed)
    Abstract [en]

    Classical swine fever (CSF), caused by CSF virus (CSFV), is considered one of the most important infectious diseases with devasting consequences for the pig industry. Recent reports describe the emergence of new CSFV-strains resulting from the action of positive selection pressure, due mainly to the bottleneck effect generated by ineffective vaccination. Even though a decrease in the genetic diversity of the positive selected CSFV-strains has been observed by several research groups, there is little information about the effect of this selective force on the virulence degree, antigenicity and pathogenicity of this type of strains. Hence, the aim of the current study was to determine the effect of the positive selection pressure on these three parameters of CSFV-strains, emerged as result of the bottleneck effects induced by unproper vaccination in a CSF-endemic area. Moreover, the effect of the positive selected strains on the epidemiological surveillance system was assessed. By the combination of in vitro, in vivo and immunoinformatic approaches we revealed that the action of the positive selection pressure induces a decrease in virulence and alteration in pathogenicity and antigenicity. However, we also noted that the evolutionary process of CSFV, especially in segregated microenvironments, could contribute to the gain-fitness event, restoring the highly virulent pattern of the circulating strains. Besides, we denoted that the presence of low virulent strains selected by bottleneck effect after inefficient vaccination can lead to a relevant challenge for the epidemiological surveillance of CSF, contributing to under-reports of the disease, favoring the perpetuation of the virus in the field. In this study B-cell and CTL epitopes on the E2 3D-structure model were also identified. Thus, the current study provides novel and significant insights into variation in virulence, pathogenesis and antigenicity experienced by CSFV strains after the positive selection pressure effect.

  • 62.
    Cristea, Alexander
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Effects of Ageing and Physical Activity on Regulation of Muscle Contraction2008Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The aims of this study were to investigate the mechanisms underlying (1) the ageing-related motor handicap at the whole muscle, cellular, contractile protein and myonuclear levels; and (2) ageing-related differences in muscle adaptability.

    In vivo muscles function was studied in the knee extensors. Decreases were observed in isokinetic and isometric torque outputs in old age in the sedentary men and women and elite master sprinters. A 20-week long specific sprint and resistance training successfully improved the maximal isometric force and rate of force development in a subgroup of master sprinters.

    In vitro measurements were performed in muscle biopsies from the vastus lateralis muscle. Immunocytochemical and contractile measurements in single membrane permeabilized muscle fibres demonstrated ageing- and gender-related changes at the myofibrillar level. In sedentary subjects, data showed a preferential decrease in the size of muscle fibres expressing type IIa MyHC in men, lower force generating capacity in muscle fibres expressing the type I MyHC isoform in both men and women and lower maximum velocity of unloaded shortening (V0) in fibres expressing types I and IIa MyHC isoforms in both men and women. The master sprinters also experienced the typical ageing-related reduction in the size of fast-twitch fibres, a shift toward a slower MyHC isoform profile and a lower V0 of type I MyHC fibres, which played a role in the decline in explosive force production capacity. The fast-twitch fibre area increased after the resistance training period. A model combining single muscle fibre confocal microscopy with a novel algorithm for 3D imaging of myonuclei in single muscle fibre segments was introduced to study the spatial organisation of myonuclei and the size of individual myonuclear domains (MNDs). Significant changes in the MND size variability and myonuclear organization were observed in old age, irrespective gender and fibre type. Those changes may influence the local quantity of specific proteins per muscle fibre volume by decreased and/or local cooperativity of myonuclei in a gender and muscle fibre specific manner.

    In conclusion, the ageing-related impairments in in vivo muscle function were related to significant changes in morphology, contractile protein expression and regulation at the muscle fibre level. It is suggested that the altered myonuclear organisation observed in old age impacts on muscle fibre protein synthesis and degradation with consequences for the ageing-related changes in skeletal muscle structure and function. However, the improved muscle function in response to a 20-week intense physical training regime in highly motivated physically active old subjects demonstrates that all ageing-related in muscle function are not immutable.

  • 63.
    Dahlgren, David
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Roos, Carl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Johansson, Pernilla
    AstraZeneca R&D, SE-43150 Gothenburg, Sweden..
    Lundqvist, Anders
    AstraZeneca R&D, SE-43150 Gothenburg, Sweden..
    Tannergren, Christer
    AstraZeneca R&D, SE-43150 Gothenburg, Sweden..
    Abraharnsson, Bertil
    AstraZeneca R&D, SE-43150 Gothenburg, Sweden..
    Sjögren, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Lennernäs, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Regional Intestinal Permeability in Dogs: Biopharmaceutical Aspects for Development of Oral Modified-Release Dosage Forms2016In: Molecular Pharmaceutics, ISSN 1543-8384, E-ISSN 1543-8392, Vol. 13, no 9, p. 3022-3033Article in journal (Refereed)
    Abstract [en]

    The development of oral modified-release (MR) dosage forms requires an active pharmaceutical ingredient (API) with a sufficiently high absorption rate in both the small and large intestine. Dogs are commonly used in preclinical evaluation of regional intestinal absorption and in the development of novel MR dosage forms. This study determined regional intestinal effective permeability (P-eff) in dogs with the aim to improve regional Peff prediction in humans. Four model drugs, atenolol, enalaprilat, metoprolol, and ketoprofen, were intravenously and regionally dosed twice as a solution into the proximal small intestine (P-SI) and large intestine (LI) of three dogs with intestinal stomas. Based on plasma data from two separate study occasions for each dog, regional Peff values were calculated using a validated intestinal deconvolution method. The determined mean P-eff values were 0.62, 0.14, 1.06, and 3.66 X 10(-4) cm/s in the P-SI, and 0.13, 0.02, 1.03, and 2.20 X 10(-4) cm/s in the LI, for atenolol, enalaprilat, metoprolol, and ketoprofen, respectively. The determined P-SI Peff values in dog were highly correlated (R-2 = 0.98) to the historically directly determined human jejunal P-eff after a single-pass perfusion. The determined dog P-SI P-eff values were also successfully implemented in GI-Sim to predict the risk for overestimation of LI absorption of low permeability drugs. We conclude that the dog intestinal stoma model is a useful preclinical tool for determination of regional intestinal permeability. Still, further studies are recommended to evaluate additional APIs, sources of variability, and formulation types, for more accurate determination of the dog model in the drug development process.

  • 64.
    Dahlin, Anna M
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Palmqvist, Richard
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Henriksson, Maria L
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Jacobsson, Maria
    Eklöf, Vincy
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Rutegård, Jörgen
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Öberg, Åke
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Van Guelpen, Bethany
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    The role of the CpG island methylator phenotype in colorectal cancer prognosis depends on microsatellite instability screening status2010In: Clinical Cancer Research, ISSN 1078-0432, E-ISSN 1557-3265, Vol. 16, no 6, p. 1845-1855Article in journal (Refereed)
    Abstract [en]

    PURPOSE: The aim of this study was to relate the CpG island methylator phenotype (CIMP; characterized by extensive promoter hypermethylation) to cancer-specific survival in colorectal cancer, taking into consideration relevant clinicopathologic factors, such as microsatellite instability (MSI) screening status and the BRAF V600E mutation.

    EXPERIMENTAL DESIGN: Archival tumor samples from 190 patients from the Northern Sweden Health and Disease Study (NSHDS) and 414 patients from the Colorectal Cancer in Umeå Study (CRUMS), including 574 with cancer-specific survival data, were analyzed for an eight-gene CIMP panel using quantitative real-time PCR (MethyLight). MSI screening status was assessed by immunohistochemistry.

    RESULTS: CIMP-low patients had a shorter cancer-specific survival compared with CIMP-negative patients (multivariate hazard ratio in NSHDS, 2.01; 95% confidence interval, 1.20-3.37; multivariate hazard ratio in CRUMS, 1.48; 95% confidence interval, 1.00-2.22). This result was similar in subgroups based on MSI screening status and was statistically significant in microsatellite stable (MSS) tumors in NSHDS. For CIMP-high patients, a shorter cancer-specific survival compared with CIMP-negative patients was observed in the MSS subgroup. Statistical significance was lost after adjusting for the BRAF mutation, but the main findings were generally unaffected.

    CONCLUSIONS: In this study, we found a poor prognosis in CIMP-low patients regardless of MSI screening status, and in CIMP-high patients with MSS. Although not consistently statistically significant, these results were consistent in two separate patient groups and emphasize the potential importance of CIMP and MSI status in colorectal cancer research.

  • 65.
    Dahlström, Örjan
    et al.
    Linköping University, Department of Behavioural Sciences and Learning, Disability Research. Linköping University, The Swedish Institute for Disability Research. Linköping University, Faculty of Arts and Sciences.
    Zetterqvist, Maria
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Lundh, Lars-Gunnar
    Department of Psychology, Lund University, Lund, Sweden..
    Svedin, Carl Göran
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Child and Adolescent Psychiatry in Linköping.
    Functions of Nonsuicidal Self-Injury: Exploratory and Confirmatory Factor Analyses in a Large Community Sample of Adolescents2015In: Psychological Assessment, ISSN 1040-3590, E-ISSN 1939-134X, Vol. 27, no 1, p. 302-313Article in journal (Refereed)
    Abstract [en]

    Given that nonsuicidal self-injury (NSSI) is prevalent in adolescents, structured assessment is an essential tool to guide treatment interventions. The Functional Assessment of Self-Mutilation (FASM) is a self-report scale that assesses frequency, methods, and functions of NSSI. FASM was administered to 3,097 Swedish adolescents in a community sample. With the aim of examining the underlying factor structure of the functions of FASM in this sample, the adolescents with NSSI who completed all function items (n = 836) were randomly divided into 2 subsamples for cross-validation purposes. An exploratory factor analysis (EFA) was followed by a confirmatory factor analysis (CFA) using the mean and variance adjusted weighted least squares (WLSMV) estimator in the Mplus statistical modeling program. The results of the EFA suggested a 3-factor model (social influence, automatic functions, and nonconformist peer identification), which was supported by a good fit in the CFA. Factors differentiated between social/interpersonal and automatic/intrapersonal functions. Based on learning theory and the specific concepts of negative and positive reinforcement, the nonconformist peer identification factor was then split into 2 factors (peer identification and avoiding demands). The resulting 4-factor model showed an excellent fit. Dividing social functions into separate factors (social influence, peer identification, and avoiding demands) can be helpful in clinical practice, where the assessment of NSSI functions is an important tool with direct implications for treatment.

  • 66.
    Danielsson-Tham, Marie-Louise
    Department of Food Hygiene, Faculty of Veterinary Medicine, Swedish University of Agricultural Sciences, Uppsala, Sweden.
    Den veterinäre livsmedelshygienikern: från patolog till risk- och faroanaytiker2004In: Svensk veterinärtidning, ISSN 0346-2250, Vol. 56, no 10, p. 19-23Article in journal (Other academic)
  • 67.
    Danielsson-Tham, Marie-Louise
    Department of Food Hygiene, Faculty of Veterinary Medicine, Swedish University of Agricultural Sciences, Uppsala, Sweden.
    Fekala funderingar2003In: Svensk veterinärtidning, ISSN 0346-2250, Vol. 55, no 15, p. 53-53Article in journal (Other (popular science, discussion, etc.))
  • 68.
    Danielsson-Tham, Marie-Louise
    Department of Food Hygiene, Faculty of Veterinary Medicine, Swedish University of Agricultural Sciences, Uppsala, Sweden.
    Hurdan veterinär vill det svenska samhället ha?2004In: Svensk veterinärtidning, ISSN 0346-2250, Vol. 56, no 1, p. 39-41Article in journal (Other (popular science, discussion, etc.))
  • 69.
    Danielsson-Tham, Marie-Louise
    Department of Food Hygiene, Faculty of Veterinary Medicine, Swedish University of Agricultural Sciences, Uppsala, Sweden.
    Köttkontrollens historia: från allmänna slakthus till Livsmedelsverket2003In: Vår Föda, no 5, p. 20-25Article in journal (Refereed)
  • 70.
    Danielsson-Tham, Marie-Louise
    Department of Food Hygiene, Faculty of Veterinary Medicine, Swedish University of Agricultural Sciences, Uppsala, Sweden.
    Mjölkontrollens historia: förfalskad grädde och TBC – problem på 1800-talet2003In: Vår Föda, ISSN 0042-2657, no 6, p. 12-14Article in journal (Refereed)
  • 71.
    Danielsson-Tham, Marie-Louise
    Department of Food Hygiene, Faculty of Veterinary Medicine, SLU, Uppsala, Sweden.
    Rapport från veterinärutbildningens nya antagningssystem2000In: Svensk veterinärtidning, ISSN 0346-2250, Vol. 52, no 14, p. 781-782Article in journal (Other academic)
  • 72.
    Danielsson-Tham, Marie-Louise
    Örebro University, School of Hospitality, Culinary Arts & Meal Science.
    Salmonella i avloppsvatten och slam1978In: XIII Nordiska Veterinärkongressen, Pohjoismainen Eläninlääkärrikongressi: Turko – Åbo, 19–22 July, 1978, FÖREDRAG OCH RAPPORTER, Esitelemät ja raportit, Prodeedings, / [ed] Bengt Westerling Toim., Helsinki: Nordiska Veterinärkongressen , 1978, p. 102-103Conference paper (Refereed)
  • 73. Davies, Brandon S J
    et al.
    Beigneux, Anne P
    Barnes, Richard H
    Tu, Yiping
    Gin, Peter
    Weinstein, Michael M
    Nobumori, Chika
    Nyrén, Rakel
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Physiological chemistry.
    Goldberg, Ira
    Olivecrona, Gunilla
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Physiological chemistry.
    Bensadoun, André
    Young, Stephen G
    Fong, Loren G
    GPIHBP1 is responsible for the entry of lipoprotein lipase into capillaries.2010In: Cell metabolism, ISSN 1932-7420, Vol. 12, no 1, p. 42-52Article in journal (Refereed)
    Abstract [en]

    The lipolytic processing of triglyceride-rich lipoproteins by lipoprotein lipase (LPL) is the central event in plasma lipid metabolism, providing lipids for storage in adipose tissue and fuel for vital organs such as the heart. LPL is synthesized and secreted by myocytes and adipocytes, but then finds its way into the lumen of capillaries, where it hydrolyzes lipoprotein triglycerides. The mechanism by which LPL reaches the lumen of capillaries has remained an unresolved problem of plasma lipid metabolism. Here, we show that GPIHBP1 is responsible for the transport of LPL into capillaries. In Gpihbp1-deficient mice, LPL is mislocalized to the interstitial spaces surrounding myocytes and adipocytes. Also, we show that GPIHBP1 is located at the basolateral surface of capillary endothelial cells and actively transports LPL across endothelial cells. Our experiments define the function of GPIHBP1 in triglyceride metabolism and provide a mechanism for the transport of LPL into capillaries.

  • 74. de Veer, Simon J.
    et al.
    Swedberg, Joakim E.
    Akcan, Muharrem
    Rosengren, K. Johan
    Brattsand, Maria
    Umeå University, Faculty of Medicine, Department of Medical Biosciences.
    Craik, David J.
    Harris, Jonathan M.
    Engineered protease inhibitors based on sunflower trypsin inhibitor-1 (SFTI-1) provide insights into the role of sequence and conformation in Laskowski mechanism inhibition2015In: Biochemical Journal, ISSN 0264-6021, E-ISSN 1470-8728, Vol. 469, no 2, p. 243-253Article in journal (Refereed)
    Abstract [en]

    Laskowski inhibitors regulate serine proteases by an intriguing mode of action that involves deceiving the protease into synthesizing a peptide bond. Studies exploring naturally occurring Laskowski inhibitors have uncovered several structural features that convey the inhibitor's resistance to hydrolysis and exceptional binding affinity. However, in the context of Laskowski inhibitor engineering, the way that various modifications intended to fine-tune an inhibitor's potency and selectivity impact on its association and dissociation rates remains unclear. This information is important as Laskowski inhibitors are becoming increasingly used as design templates to develop new protease inhibitors for pharmaceutical applications. In this study, we used the cyclic peptide, sunflower trypsin inhibitor-1 (SFTI-1), as a model system to explore how the inhibitor's sequence and structure relate to its binding kinetics and function. Using enzyme assays, MD simulations and NMR spectroscopy to study SFTI variants with diverse sequence and backbone modifications, we show that the geometry of the binding loop mainly influences the inhibitor's potency by modulating the association rate, such that variants lacking a favourable conformation show dramatic losses in activity. Additionally, we show that the inhibitor's sequence (including both the binding loop and its scaffolding) influences its potency and selectivity by modulating both the association and the dissociation rates. These findings provide new insights into protease inhibitor function and design that we apply by engineering novel inhibitors for classical serine proteases, trypsin and chymotrypsin and two kallikrein-related peptidases (KLK5 and KLK14) that are implicated in various cancers and skin diseases.

  • 75.
    Degerman, Sofie
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Landfors, Mattias
    Umeå University, Faculty of Science and Technology, Department of Mathematics and Mathematical Statistics. Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Siwicki, Jan Konrad
    Revie, John
    Borssen, Magnus
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Evelönn, Emma
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Forestier, Erik
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Medical and Clinical Genetics.
    Chrzanowska, Krystyna H.
    Ryden, Patrik
    Umeå University, Faculty of Science and Technology, Department of Mathematics and Mathematical Statistics.
    Keith, W. Nicol
    Roos, Göran
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Immortalization of T-Cells Is Accompanied by Gradual Changes in CpG Methylation Resulting in a Profile Resembling a Subset of T-Cell Leukemias2014In: Neoplasia, ISSN 1522-8002, E-ISSN 1476-5586, Vol. 16, no 7, p. 606-615Article in journal (Refereed)
    Abstract [en]

    We have previously described gene expression changes during spontaneous immortalization of T-cells, thereby identifying cellular processes important for cell growth crisis escape and unlimited proliferation. Here, we analyze the same model to investigate the role of genome-wide methylation in the immortalization process at different time points pre-crisis and post-crisis using high-resolution arrays. We show that over time in culture there is an overall accumulation of methylation alterations, with preferential increased methylation close to transcription start sites (TSSs), islands, and shore regions. Methylation and gene expression alterations did not correlate for the majority of genes, but for the fraction that correlated, gain of methylation close to TSS was associated with decreased gene expression. Interestingly, the pattern of CpG site methylation observed in immortal T-cell cultures was similar to clinical T-cell acute lymphoblastic leukemia (T-ALL) samples classified as CpG island methylator phenotype positive. These sites were highly overrepresented by polycomb target genes and involved in developmental, cell adhesion, and cell signaling processes. The presence of non-random methylation events in in vitro immortalized T-cell cultures and diagnostic T-ALL samples indicates altered methylation of CpG sites with a possible role in malignant hematopoiesis.

  • 76.
    Dencker, Lennart
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Hellmann, K.
    Klifovet AG, Geyerspergerstr 27, D-80689 Munich, Germany..
    Mochel, J.
    Leiden Acad Ctr Drug Res, Dept Pharmacol, NL-2300 Leiden, Netherlands..
    Senel, S.
    Hacettepe Univ, Fac Pharm, Dept Pharmaceut Technol, TR-06100 Ankara, Turkey..
    Tyden, E.
    Swedish Univ Agr Sci, Dept Biomed Sci & Vet Publ Hlth, Div Parasitol, Box 7036, S-75007 Uppsala, Sweden..
    Vendrig, J. C.
    Univ Utrecht, Fac Vet Med, Inst Risk Assessment Sci Vet Pharmacol Pharmacoth, Yalelaan 104,Postbus 80152, NL-3584 CM Utrecht, Netherlands..
    Linden, H.
    EUFEPS, Veddesta Business Ctr, SE-17572 Jarfalla, Stockholm, Sweden..
    Schmerold, I.
    Univ Vet Med Vienna, A-1020 Vienna, Austria.;Obere Donaustr 21-3-4, A-1020 Vienna, Austria..
    Position Paper: EUFEPS Network on Veterinary Medicines Initiative: An interdisciplinary forum to support Veterinary Pharmacology and promote the development of new pharmaceuticals for Animal Health2016In: European Journal of Pharmaceutical Sciences, ISSN 0928-0987, E-ISSN 1879-0720, Vol. 91, p. I-VIIArticle in journal (Refereed)
    Abstract [en]

    Veterinary medicines account for a substantial portion of the production, sale, and consumption of medicines in Europe, and probably world-wide. This calls our attention to the fact that only healthy farm animals can ensure safe and sufficient livestock products to meet the growing demand for animal protein. Human and veterinary medicine share many common features - expressed and symbolised by the "One Health Concept". This concept forms the logical basis for the maintenance of healthy livestock by the control of zoonoses and foodborne diseases, the prevention of poor sanitary conditions, and the reduction of microbial and parasitic threats, including resistance to antibiotics and anti-parasitic drugs. Achieving these aims will require international cooperation and interdisciplinary action. A new initiative of the European Federation for Pharmaceutical Sciences (EUFEPS) - the Network on Veterinary Medicines - has the potential to manage and overcome these challenges. A number of EUFEPS expertise networks have already been established, and some will be instrumental in supporting the activities of the Network on Veterinary Medicines, e.g., the European Network on PharmacoGenomics Research and Implementation (EPRIN), as well as the Network on Bioavailability and Biopharmaceutics, and the envisioned Network on Systems Pharmacology. Notably, the EUFEPS Networks on Safety Sciences, on Environment and Pharmaceuticals and on NanoMedicine as well as on Regulatory Science, represent promising partners. New technologies are being introduced to veterinary medicine for the treatment of numerous and frequently species-specific conditions. Scientific input from different areas is required to evaluate the potential benefitrisk profiles of these novel products, drug delivery techniques, and medical attention for animals as a whole. Drug treatment of food-producing animals inevitably affects consumer safety and public health, as any administration of medicines to animals may result in the presence of drug residues in edible tissues or products such as milk, eggs, and honey. The many questions surrounding the risks to human health and to the environment posed by exposure to veterinary drug residues cause great concern among health authorities as well as the public. In particular, the shared use of many classes of antimicrobials in both veterinary and human medicine, the emergence and spread of resistant microbes from animals or animal-derived products to humans, and the presence of contaminated manure in the environment are all provoking deep concern throughout the world. The Network on Veterinary Medicines initiative sees itself as broadly positioned. Among its most important goals are contributing to legislative issues in veterinary medicine and to the development of new pharmaceuticals for animal health, including novel drug delivery systems. Efforts to support the academic teaching and training of veterinary professionals and formulators for veterinary drug delivery are also considered imperative objectives of the network. The pursuit of these tasks will depend on interdisciplinary cooperation among experts from pharmaceutical and veterinary sciences, concentrating on issues where scientists from academia, industry and regulatory agencies can collaborate. National and international healthcare bodies, as well as organisations dedicated to the endorsement of teaching and training of scientists in pharmaceutical and veterinary sciences, are also key partners. Major objectives of the network include the following: strengthening academic research to promote the emergence of new concepts, principles and mechanisms of action to develop innovative new veterinary medicinal products, supporting the education and training of future healthcare professionals in veterinary practice, pharmacy and industrial research, including continuing professional development, and supporting Veterinary Universities. Further efforts of the Network will encourage the European Commission to initiate calls for research in the area of veterinary medicines, such as Horizon 2020. Once these calls are in place, the formation of strong consortia to apply for funding (IMI, EU-funding) is projected. The success of the Network depends on the engagement and expertise of cooperating specialists. It will benefit from the experience and means of other EUFEPS networks.

  • 77.
    Devad, Martin
    et al.
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences.
    Wallin, Peter
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences.
    Kosttillskott åt folket?!: en kvantitativ studie om användandet av och åsikter om kosttillskott2007Independent thesis Basic level (degree of Bachelor), 10 poäng / 15 hpStudent thesis
    Abstract [sv]

    Syfte & frågeställningar

    Syftet var att undersöka användandet av och uppfattningar om kosttillskott bland människor som tränar på gym. Frågeställningarna löd enligt följande:

    - Vilka kategorier av människor som tränar på gym använder kosttillskott?

    - Skiljer sig åsikterna om kosttillskott beroende på om man använder det eller inte?

    - Har användandet av kosttillskott någon inverkan på attityden till dopning?

    Metod

    Studien baseras på en kvantitativ enkätundersökning vilken utfördes på fyra olika gym inom Storstockholm. Tre utav gymmen representeras av två stora kedjor och det fjärde av ett mindre gym, vilket inte ingick i någon kedja. Gymmen selekterades genom att ta fram de två stora gymkedjornas samtliga anläggningar inom stor Stockholm och sedan numrera dessa varpå lottdragning utfördes. Samma procedur genomfördes gällande det mindre gymmet. Individerna som kom att delta i studien blev 169st varav 105 män och 64 kvinnor. Dessa selekterades genom ett frivilligt urval i samband med att de utvalda gymmen besöktes. Datan analyserades i SPSS där vi använt ett chi-2- samt Man Whitney U- test.

    Resultat

    Resultaten visade att användandet av kosttillskott var störst bland styrketränande män vilkas huvudmål med träningen var att förbättra hälsan samt bygga muskler. Åsikterna om kosttillskott skilde sig åt beroende på om respondenterna använde det eller inte. Detta framkom då de respondenter som nyttjade kosttillskott såg fler fördelar och hade en positivare inställning till användandet. I studien framkom det att majoriteten (85.1 %, n = 168) av respondenterna var emot användandet av dopning. Bland användarna var det 26.7 % (n = 75) som ansåg att det var upp till individen att bestämma om denne ville nyttja dopning.

    Slutsats

    Användandet av kosttillskott var förhållandevis stort då 44,9 % av respondenterna använde det mer eller mindre regelbundet. Majoriteten (59,6 %) av respondenterna uppgav att det var upp till individen att bestämma om denne ville nyttja kosttillskott. Tron på att kosttillskott ger effekt på träningen men att det kan bli skadligt vid överdosering delades också av majoriteten (54,8 %) av respondenterna.

  • 78.
    Doane, Marie
    et al.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Biology and Environmental Science.
    Sarenbo, Sirkku
    Linnaeus University, Faculty of Health and Life Sciences, Department of Biology and Environmental Science.
    An eradication attempt of Mycoplasma spp. mastitis at a large dairy farm in NY State, USA2015In: IOCH 2015, 2015Conference paper (Refereed)
  • 79.
    Doane, Marie
    et al.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Biology and Environmental Science.
    Sarenbo, Sirkku
    Linnaeus University, Faculty of Health and Life Sciences, Department of Biology and Environmental Science.
    Antibiotic usage in 2013 on a dairy CAFO in NY State, USA2014In: Infection Ecology & Epidemiology, ISSN 2000-8686, E-ISSN 2000-8686, Vol. 4, p. Articel ID: 24259-Article in journal (Refereed)
    Abstract [en]

    Antimicrobial resistance is threatening humans and animals worldwide. Biosecurity and 1-year usage of antibiotics on a dairy concentrated animal feeding operation (CAFO) in NY State, USA, were mapped: how much antibiotics were used, for what purpose, and whether any decrease could be warranted. Approximately 493 kg antibiotics was used, of which 376 kg was ionophores (monensin and lasalocides), 79 kg penicillin, 16.5 kg lincosamides, 8.0 kg aminoglycosides, 7.7 kg sulfamides, 3.4 kg cephalosporin, 2 kg macrolides, 0.7 kg amphenicols, and 0.1 kg fluoroquinolones. Usage reduction by 84% was realistic without compromising the animal welfare. Further reduction could be possible by improving the biosecurity and by utilizing antibiotic sensitivity testing.

  • 80. Drager, Luciano F.
    et al.
    Li, Jianguo
    Shin, Mi-Kyung
    Reinke, Christian
    Aggarwal, Neil R.
    Jun, Jonathan C.
    Bevans-Fonti, Shannon
    Sztalryd, Carole
    OByrne, Sheila M.
    Kroupa, Olessia
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Physiological chemistry.
    Olivecrona, Gunilla
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Physiological chemistry.
    Blaner, William S.
    Polotsky, Vsevolod Y.
    Intermittent hypoxia inhibits clearance of triglyceride-rich lipoproteins and inactivates adipose lipoprotein lipase in a mouse model of sleep apnoea2012In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 33, no 6, p. 783-U33Article in journal (Refereed)
    Abstract [en]

    Delayed lipoprotein clearance is associated with atherosclerosis. This study examined whether chronic intermittent hypoxia (CIH), a hallmark of obstructive sleep apnoea (OSA), can lead to hyperlipidaemia by inhibiting clearance of triglyceride rich lipoproteins (TRLP). Male C57BL/6J mice on high-cholesterol diet were exposed to 4 weeks of CIH or chronic intermittent air (control). FIO2 was decreased to 6.5 once per minute during the 12 h light phase in the CIH group. After the exposure, we measured fasting lipid profile. TRLP clearance was assessed by oral gavage of retinyl palmitate followed by serum retinyl esters (REs) measurements at 0, 1, 2, 4, 10, and 24 h. Activity of lipoprotein lipase (LpL), a key enzyme of lipoprotein clearance, and levels of angiopoietin-like protein 4 (Angptl4), a potent inhibitor of the LpL activity, were determined in the epididymal fat pads, skeletal muscles, and heart. Chronic intermittent hypoxia induced significant increases in levels of total cholesterol and triglycerides, which occurred in TRLP and LDL fractions (P 0.05 for each comparison). Compared with control mice, animals exposed to CIH showed increases in REs throughout first 10 h after oral gavage of retinyl palmitate (P 0.05), indicating that CIH inhibited TRLP clearance. CIH induced a 5-fold decrease in LpL activity (P 0.01) and an 80 increase in Angptl4 mRNA and protein levels in the epididymal fat, but not in the skeletal muscle or heart. CIH decreases TRLP clearance and inhibits LpL activity in adipose tissue, which may contribute to atherogenesis observed in OSA.

  • 81. Drögemüller, Cord
    et al.
    Becker, Doreen
    Kessler, Barbara
    Kemter, Elisabeth
    Tetens, Jens
    Jurina, Konrad
    Jäderlund, Karin Hultin
    Flagstad, Annette
    Perloski, Michele
    Lindblad-Toh, Kerstin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Matiasek, Kaspar
    A deletion in the N-myc downstream regulated gene 1 (NDRG1) gene in Greyhounds with polyneuropathy2010In: PloS one, ISSN 1932-6203, Vol. 5, no 6, p. e11258-Article in journal (Refereed)
    Abstract [en]

    The polyneuropathy of juvenile Greyhound show dogs shows clinical similarities to the genetically heterogeneous Charcot-Marie-Tooth (CMT) disease in humans. The pedigrees containing affected dogs suggest monogenic autosomal recessive inheritance and all affected dogs trace back to a single male. Here, we studied the neuropathology of this disease and identified a candidate causative mutation. Peripheral nerve biopsies from affected dogs were examined using semi-thin histology, nerve fibre teasing and electron microscopy. A severe chronic progressive mixed polyneuropathy was observed. Seven affected and 17 related control dogs were genotyped on the 50k canine SNP chip. This allowed us to localize the causative mutation to a 19.5 Mb interval on chromosome 13 by homozygosity mapping. The NDRG1 gene is located within this interval and NDRG1 mutations have been shown to cause hereditary motor and sensory neuropathy-Lom in humans (CMT4D). Therefore, we considered NDRG1 a positional and functional candidate gene and performed mutation analysis in affected and control Greyhounds. A 10 bp deletion in canine NDRG1 exon 15 (c.1080_1089delTCGCCTGGAC) was perfectly associated with the polyneuropathy phenotype of Greyhound show dogs. The deletion causes a frame shift (p.Arg361SerfsX60) which alters several amino acids before a stop codon is encountered. A reduced level of NDRG1 transcript could be detected by RT-PCR. Western blot analysis demonstrated an absence of NDRG1 protein in peripheral nerve biopsy of an affected Greyhound. We thus have identified a candidate causative mutation for polyneuropathy in Greyhounds and identified the first genetically characterized canine CMT model which offers an opportunity to gain further insights into the pathobiology and therapy of human NDRG1 associated CMT disease. Selection against this mutation can now be used to eliminate polyneuropathy from Greyhound show dogs.

  • 82.
    du Preez, Marinus
    et al.
    North-West University, South Africa.
    Govender, Danny
    South African National Parks, South Africa.
    Kylin, Henrik
    Linköping University, Department of Thematic Studies, Tema Environmental Change. Linköping University, Faculty of Arts and Sciences.
    Bouwman, Hindrik
    North-West University, South Africa.
    Metallic elements in Nile Crocodile eggs from the Kruger National Park, South Africa2018In: Ecotoxicology and Environmental Safety, ISSN 0147-6513, E-ISSN 1090-2414, Vol. 148, p. 930-941Article in journal (Refereed)
    Abstract [en]

    The Nile Crocodile is the largest predator on the African continent. Recent mass mortalities in the Kruger National Park (KNP) raised concerns about possible influence of pollution. We analysed eggs and their eggshells collected from nests inside the KNP and from a crocodile farm for metallic elements. We found that mercury, selenium, and copper occurred at levels of concern. Eggshells had very high concentrations of iron. Apart from toxicological implications associated with elevated concentrations in eggs, we found iron possibly contributing towards thicker eggshells. Thicker shells may act as a barrier to gas and water exchange, as well as possibly increasing the effort required for the hatchling to emerge from tightly packed shells under sand. Pollutants are transported into the KNP via rivers, and possibly via air. Mercury and copper pollution are waste-, industrial- and mining-related; ecotoxicological concern should therefore be extended to all areas where the four African crocodile species occur. Reptiles are under-represented in ecotoxicological literature in general, and especially from Africa. We know of only one previous report on metals and metalloids in crocodile eggs from Africa (Zimbabwe), published 30 years ago. Reduced fitness, endocrine disruption and effects on behaviour are other possible sub-lethal effects associated with metallic elements that may only become apparent decades later in a long-lived species such as the Nile Crocodile. In the face of habitat destruction, pollution, human population increases, and climate change, further research is needed regarding pollutant concentrations and effects in all African reptiles . The rivers that carry water from outside the park sustain its aquatic life, but also transport pollutants into the KNP. Therefore, improved source mitigation remains an important task and responsibility for all involved.

    The full text will be freely available from 2019-12-19 15:57
  • 83.
    Dórea, Fernanda C.
    et al.
    Department of Disease Control and Epidemiology, National Veterinary Institute, Sweden.
    Vial, Flavie
    Epi-Connect, Skogås, Sweden.
    Hammar, Karl
    Linköping University, Department of Computer and Information Science, Human-Centered systems. Linköping University, Faculty of Science & Engineering. Department of Computer Science and Informatics, Jönköping University, Sweden.
    Lindberg, Ann
    Department of Disease Control and Epidemiology, National Veterinary Institute, Sweden.
    Lambrix, Patrick
    Linköping University, Department of Computer and Information Science, Database and information techniques. Linköping University, Faculty of Science & Engineering.
    Blomqvist, Eva
    Linköping University, Department of Computer and Information Science, Human-Centered systems. Linköping University, Faculty of Science & Engineering.
    Revie, Crawford W.
    Atlantic Veterinary College, University of Prince Edward Island, Canada.
    Drivers for the development of an Animal Health Surveillance Ontology (AHSO)2019In: Preventive Veterinary Medicine, ISSN 0167-5877, E-ISSN 1873-1716, Vol. 166, no 1, p. 39-48Article in journal (Refereed)
    Abstract [en]

    Comprehensive reviews of syndromic surveillance in animal health have highlighted the hindrances to integration and interoperability among systems when data emerge from different sources. Discussions with syndromic surveillance experts in the fields of animal and public health, as well as computer scientists from the field of information management, have led to the conclusion that a major component of any solution will involve the adoption of ontologies. Here we describe the advantages of such an approach, and the steps taken to set up the Animal Health Surveillance Ontological (AHSO) framework. The AHSO framework is modelled in OWL, the W3C standard Semantic Web language for representing rich and complex knowledge. We illustrate how the framework can incorporate knowledge directly from domain experts or from data-driven sources, as well as by integrating existing mature ontological components from related disciplines. The development and extent of AHSO will be community driven and the final products in the framework will be open-access.

  • 84.
    Ebrahimi, Majid
    Umeå University, Faculty of Medicine, Department of Odontology.
    Studies of p63 and p63 related proteins in patients diagnosed with oral lichen planus2007Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Oral lichen planus (OLP) is a chronic inflammatory disease of the oral mucosa and also one of the more common mucosal conditions mostly affecting middle aged individuals. Even though OLP is well investigated the etiology of this disease is still unknown, even if autoimmunity as a possible etiologic factor has been suggested. WHO classifies OLP as a pre malignant condition but malignant transformation of OLP is a matter of great controversy. The p53 protein is a tumour suppressor with the potential to induce apoptosis or cell cycle arrest of DNA damaged cells. Another member of the p53 family, p63, comprises six different isoforms, and plays a crucial role in the formation of oral mucosa, salivary glands, teeth and skin. p63 has also been suggested to be involved in development of squamous cell carcinoma of the head and neck (SCCHN). β-catenin, E-cadherin and epidermal growth factor receptor (EGFR) are p63 related proteins and abnormalities in their expression are suggested to be involved in development of SCCHN.

    Methods. Using immunohistochemistry and antibodies directed against p53 and those distinguishing between the p63 isoforms we analysed biopsies of OLP, SCCHN and normal oral tissue. We also mapped levels of p63 and p53 isoforms using RT-PCR technique. Furthermore expression of the p63 related proteins β-catenin, E-cadherin and EGFR was studied using immunoblot analysis. In an attempt to investigate autoimmunity as a causative factor of OLP we analysed sera from patients diagnosed with OLP and matched control individuals in order to see if there were autoantibodies directed against the p53 family.

    Results. When mapping p53 and p63 protein status decreased expression of p63 and increased expression of p53 was seen in OLP compared to normal tissue. In accordance with these results, levels of p63 RNA were also lower in OLP lesions compared with normal tissue. Concerning p53 isoforms, the “original” p53 isoform was expressed in all OLP lesions and normal control tissue. Of the other isoforms, p53β and Δ133p53 were expressed in the majority of samples. Our results regarding p63 related proteins showed a generally lower expression of these proteins in OLP lesions compared to normal control tissue. When studying sera from patients with OLP we found circulating autoantibodies against all six p63 and four p73 isoforms in two patients.

    Conclusions. The potential for malignant transformation of OLP is still a subject of discussion and rather controversial. While some of our results regarding status of p53 and p63 both at protein and RNA levels support this theory, other results concerning for example p63 related proteins point in the opposite direction. Based on our studies it is thus not possible to either support nor contradict the statement that OLP is a clear-cut premalignant condition. In our effort to understand the etiology of OLP we were the first to demonstrate autoantibodies against p63 and p73 in what could be a subgroup of OLP patients. OLP could thus be suggested to be not one distinct disease, but based on our data a disease comprising different subgroups.

  • 85.
    Edfors, Inger
    et al.
    Linnaeus University, Faculty of Science and Engineering, School of Natural Sciences.
    Torremorrel, M
    Univ Minnesota.
    Escherichia coli and Salmonella in pigs2010In: Breeding for Disease Resistance in Farm Animals / [ed] RFA Axford, S Bishop, F Nicholas, JB Owen, Walllingford, UK: CABI Publishing, 2010, 3rd, p. 232-250Chapter in book (Other academic)
    Abstract [en]

    Diarrhoea due to bacterial infections is a problem mainly in the young growing animal, including the pig. Among the bacteria that cause diarrhoea in pigs are various strains of Escherichia coli and Salmonella. Considerable genetic variation in resistance/susceptibility has been found for both neonatal and post-weaning diarrhoea caused by E. coli carrying F4 fimbriae and post-weaning diarrhoea and oedema disease due to E. coli strains with F18 fimbriae. The loci for the receptors of both types of fimbriae have been mapped: the F4 receptor(s) to chromosome 13 (SSC13) and the F18 receptor to chromosome 6 (SSC6). Several candidate genes have been suggested for the F4 receptor, among them different mucine genes (MUC4, MUC13), and a very close association between a single-nucleotide polymorphism (SNP) in an alpha (1, 2) fucosyltransferase gene (FUT1) and the F18 receptor has been identified.Resistance to Salmonella infections in mice is associated with the antimicrobial activity of macrophages, and some studies have suggested that it is linked with polymorphism in the Nramp1 gene. The gene has been identified in several species including the pig, but data are so far lacking concerning association between polymorphism in the porcine gene and resistance-susceptibility to Salmonella infection. Using transcriptome profiles, several porcine genes that are differentially up or downregulated during Salmonella infection have been identified. Further studies of associations between polymorphisms in these genes and the outcome of Salmonella infection may facilitate the development of tools to identify carrier pigs, and lead towards identification of markers that can be used to select for resistant pigs.Breeding for increased disease resistance can be potentially performed in several ways; excluding susceptible breeding of animals after exposure, marker-assisted selection (MAS) based on closely linked loci or direct selection based on polymorphism in the causative gene. The rapid development in molecular genetics has provided dense genome maps and the tools to identify and study individual genes, both at the deoxyribonuclease acid (DNA) and the expression level. Overall use of genetic markers influencing disease traits is expected to increase significantly in the coming years. This number will grow as large-scale accurate disease phenotypes are collected in pedigreed populations. It is likely that many disease markers will contribute additively to the selection criteria and will be used as part of complex selection indices that will balance other economically significant traits.

  • 86. Edner, Anna H.
    et al.
    Essén-Gustavsson, Birgitta
    Nyman, Görel C.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Metabolism during anaesthesia and recovery in colic and healthy horses: a microdialysis study2009In: Acta Veterinaria Scandinavica, ISSN 1751-0147, E-ISSN 1751-0147, Vol. 51, no 1, p. 10-Article in journal (Refereed)
    Abstract [en]

    Background: Muscle metabolism in horses has been studied mainly by analysis of substances in blood or plasma and muscle biopsy specimens. By using microdialysis, real-time monitoring of the metabolic events in local tissue with a minimum of trauma is possible. There is limited information about muscle metabolism in the early recovery period after anaesthesia in horses and especially in the colic horse. The aims were to evaluate the microdialysis technique as a complement to plasma analysis and to study the concentration changes in lactate, pyruvate, glucose, glycerol, and urea during anaesthesia and in the recovery period in colic horses undergoing abdominal surgery and in healthy horses not subjected to surgery. Methods: Ten healthy university-owned horses given anaesthesia alone and ten client-owned colic horses subjected to emergency abdominal surgery were anaesthetised for a mean (range) of 230 min (193-273) and 208 min (145-300) respectively. Venous blood samples were taken before anaesthesia. Venous blood sampling and microdialysis in the gluteal muscle were performed during anaesthesia and until 24 h after anaesthesia. Temporal changes and differences between groups were analysed with an ANOVA for repeated measures followed by Tukey Post Hoc test or Planned Comparisons. Results: Lactate, glucose and urea, in both dialysate and plasma, were higher in the colic horses than in the healthy horses for several hours after recovery to standing. In the colic horses, lactate, glucose, and urea in dialysate, and lactate in plasma increased during the attempts to stand. The lactate-to-pyruvate ratio was initially high in sampled colic horses but decreased over time. In the colic horses, dialysate glycerol concentrations varied considerably whereas in the healthy horses, dialysate glycerol was elevated during anaesthesia but decreased after standing. In both groups, lactate concentration was higher in dialysate than in plasma. The correspondence between dialysate and plasma concentrations of glucose, urea and glycerol varied. Conclusion: Microdialysis proved to be suitable in the clinical setting for monitoring of the metabolic events during anaesthesia and recovery. It was possible with this technique to show greater muscle metabolic alterations in the colic horses compared to the healthy horses in response to regaining the standing position.

  • 87. Edner, Anna H.
    et al.
    Nyman, Görel C.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Essén-Gustavsson, Birgitta
    Metabolism before, during and after anaesthesia in colic and healthy horses2007In: Acta Veterinaria Scandinavica, ISSN 1751-0147, E-ISSN 1751-0147, Vol. 49, no 1, p. 34-Article in journal (Refereed)
    Abstract [en]

    Background: Many colic horses are compromised due to the disease state and from hours of starvation and sometimes long trailer rides. This could influence their muscle energy reserves and affect the horses' ability to recover. The principal aim was to follow metabolic parameter before, during, and up to 7 days after anaesthesia in healthy horses and in horses undergoing abdominal surgery due to colic. Methods: 20 healthy horses given anaesthesia alone and 20 colic horses subjected to emergency abdominal surgery were anaesthetised for a mean of 228 minutes and 183 minutes respectively. Blood for analysis of haematology, electrolytes, cortisol, creatine kinase (CK), free fatty acids (FFA), glycerol, glucose and lactate was sampled before, during, and up to 7 days after anaesthesia. Arterial and venous blood gases were obtained before, during and up to 8 hours after recovery. Gluteal muscle biopsy specimens for biochemical analysis of muscle metabolites were obtained at start and end of anaesthesia and 1 h and 1 day after recovery. Results: Plasma cortisol, FFA, glycerol, glucose, lactate and CK were elevated and serum phosphate and potassium were lower in colic horses before anaesthesia. Muscle adenosine triphosphate (ATP) content was low in several colic horses. Anaesthesia and surgery resulted in a decrease in plasma FFA and glycerol in colic horses whereas levels increased in healthy horses. During anaesthesia muscle and plasma lactate and plasma phosphate increased in both groups. In the colic horses plasma lactate increased further after recovery. Plasma FFA and glycerol increased 8 h after standing in the colic horses. In both groups, plasma concentrations of CK increased and serum phosphate decreased post-anaesthesia. On Day 7 most parameters were not different between groups. Colic horses lost on average 8% of their initial weight. Eleven colic horses completed the study. Conclusion: Colic horses entered anaesthesia with altered metabolism and in a negative oxygen balance. Muscle oxygenation was insufficient during anaesthesia in both groups, although to a lesser extent in the healthy horses. The post-anaesthetic period was associated with increased lipolysis and weight loss in the colic horses, indicating a negative energy balance during the first week post-operatively.

  • 88.
    Effati, Pedram
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Survey Of Genes Of Escherichia Coli Causing Bovine Mastitis With DNA Microarrays2011Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    Background: Mastitis in dairy cattle is a common ailment worldwide. A cause of mastitis can be bacteria such as Escherichia coli. Mastitis is not a deadly ailment and sometimes the dairy cows show no symptoms but if certain virulence genes are present in the bacteria that cause the mastitis, the bacteria can be transmitted to humans and cause severe diseases. The potential presence of enterohemorrhagic Escherichia coli (EHEC) in particular would be a major concern for human health.

    Aim: The aim for this study was to analyze the presence of virulence genes known to be present in E.coli strains isolated from dairy cows with mastitis in Sweden.

    Method: A Qiagen BIO ROBOT EZ1 was used to purify DNA from 90 bacterial cultures. A panel of virulence genes were amplified and biotinylated from the purified DNA by PCR and an E.coli based DNA microarray was used to detect presumed virulence genes in E.coli.

    Result: There were no samples that had all the genes traditionally used to classify E.coli as EHEC or potential EHEC. 63 samples were analyzed without any problems but 27 samples were not fully analyzed.

    Conclusion: The DNA based microarray proved to be a reliable method to detect genes from pathogenic bacteria but it needed high concentration of purified DNA which was not always easy to obtain. There were some samples in this study that contained virulence genes.

  • 89.
    Eilertz, Ingrid
    et al.
    Department of Food Hygiene, Faculty of Veterinary Medicine, University of Agricultural Sciences, Uppsala, Sweden.
    Danielsson Tham, Marie-Louise
    Department of Food Hygiene, Faculty of Veterinary Medicine, University of Agricultural Sciences, Uppsala, Sweden.
    Hammarberg, Karl-Erik
    Department of Food Hygiene, Faculty of Veterinary Medicine, University of Agricultural Sciences, Uppsala, Sweden.
    Reeves, MW
    Rocourt, Jocelyne
    Laboratoire des Listeria, Institute Pasteur, Paris, France.
    Seeliger, HPR
    Institute für Hygiene und Mikrobiologie, Würzburg, Germany.
    Swaminathan, Balasubramanian
    Centers for Disease Control and Prevention, Atlanta GA, USA.
    Tham, Wilhelm
    Department of Food Hygiene, Faculty of Veterinary Medicine, University of Agricultural Sciences, Uppsala, Sweden.
    Isolation of Listeria monocytogenes from goat cheese associated with a case of listeriosis in goat1993In: Acta Veterinaria Scandinavica, ISSN 1751-0147, E-ISSN 1751-0147, Vol. 34, no 2, p. 145-149Article in journal (Refereed)
    Abstract [en]

    Listeria monocytogenes was isolated from the brain of a goat, which was euthanized due to listeriosis. A few weeks later a similar subtype of L. monocytogenes was isolated from an on-farm manufactured fresh cheese which did not contain any milk from the goat which had suffered from listeriosis. A similar subtype was also found on 1 of the shelves in the refrigerator where cheeses were stored. Prior to the onset of listeriosis, 1 fresh cheese had been made of milk from the actual goat, which may have excreted L. monocytogenes in her milk. Thus, the cheese made of this milk may have contaminated the shelves in the refrigerator which then has served as a Listeria reservoir for new cheeses during several weeks.

  • 90.
    Ekhtiari Bidhendi, Elaheh
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences.
    Bergh, Johan
    Umeå University, Faculty of Medicine, Department of Medical Biosciences.
    Zetterström, Per
    Umeå University, Faculty of Medicine, Department of Medical Biosciences.
    Andersen, Peter M.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Marklund, Stefan L.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences.
    Brännström, Thomas
    Umeå University, Faculty of Medicine, Department of Medical Biosciences.
    Two superoxide dismutase prion strains transmit amyotrophic lateral sclerosis-like disease2016In: Journal of Clinical Investigation, ISSN 0021-9738, E-ISSN 1558-8238, Vol. 126, no 6, p. 2249-2253Article in journal (Refereed)
    Abstract [en]

    Amyotrophic lateral sclerosis (ALS) is an adult-onset degeneration of motor neurons that is commonly caused by mutations in the gene encoding superoxide dismutase 1 (SOD1). Both patients and Tg mice expressing mutant human SOD1 (hSOD1) develop aggregates of unknown importance. In Tg mice, 2 different strains of hSOD1 aggregates (denoted A and B) can arise; however, the role of these aggregates in disease pathogenesis has not been fully characterized. Here, minute amounts of strain A and B hSOD1 aggregate seeds that were prepared by centrifugation through a density cushion were inoculated into lumbar spinal cords of 100-day-old mice carrying a human SOD1 Tg. Mice seeded with A or B aggregates developed premature signs of ALS and became terminally ill after approximately 100 days, which is 200 days earlier than for mice that had not been inoculated or were given a control preparation. Concomitantly, exponentially growing strain A and B hSOD1 aggregations propagated rostrally throughout the spinal cord and brainstem. The phenotypes provoked by the A and B strains differed regarding progression rates, distribution, end-stage aggregate levels, and histopathology. Together, our data indicate that the aggregate strains are prions that transmit a templated, spreading aggregation of hSOD1, resulting in a fatal ALS-like disease.

  • 91.
    Ekorn, Bonnie
    et al.
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences.
    Holmgren, Maria
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences.
    Frulle = full rulle?: en kvantitativ studie om frukostens inverkan på elevers fysiska prestation i ämnet idrott och hälsa2007Independent thesis Basic level (degree of Bachelor), 10 poäng / 15 hpStudent thesis
    Abstract [sv]

    Sammanfattning

    Syfte och frågeställningar

    Syftet var att undersöka om frukosten har någon inverkan på den fysiska prestationen i ämnet idrott och hälsa. Frågeställningarna var:

    • Finns det något samband mellan fysisk prestation och frukost hos elever som äter respektive inte äter frukost?

    • Är det någon skillnad i den fysiska prestationen mellan könen, bland de elever som äter respektive inte äter frukost?

    • Finns det något samband mellan fysisk prestation, tidpunkt för frukostintag och idrott och hälsa bland elever som äter respektive inte äter frukost?

    Metod

    Undersökningen är kvantitativ och har genomförts bland 89 elever i skolår 7 och 8. Det externa bortfallet var 28,8 procent. Studien genomfördes i idrott och hälsa där eleverna deltog och sedan svarade på en enkät. I statistikprogrammet SPSS fastställdes resultatet.

    Resultat

    Frukosten har en inverkan på prestationen i form av svett. De elever som äter frukost svettas mer. Det finns ingen skillnad i prestation mellan flickor och pojkar som har ätit respektive inte ätit frukost. Tidpunkten för frukostintaget har en inverkan på prestationen i form av svett. Ju kortare tid mellan frukostintag och aktivitetsutövande, desto mer svettas eleven.

    Slutsats

    Som slutsats kan vi se att frukosten har en inverkan på prestationen i form av svett. De elever som äter frukost svettas mer.

  • 92. Ekstrand, C.
    et al.
    Bondesson, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Analytical Pharmaceutical Chemistry.
    Gabrielsson, J.
    Hedeland, Mikael
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Analytical Pharmaceutical Chemistry.
    Kallings, P.
    Olsen, L.
    Ingvast-Larsson, C.
    Plasma concentration-dependent suppression of endogenous hydrocortisone in the horse after intramuscular administration of dexamethasone-21-isonicotinate2015In: Journal of Veterinary Pharmacology and Therapeutics, ISSN 0140-7783, E-ISSN 1365-2885, Vol. 38, no 3, p. 235-242Article in journal (Refereed)
    Abstract [en]

    Detection times and screening limits (SL) are methods used to ensure that the performance of horses in equestrian sports is not altered by drugs. Drug concentration-response relationship and knowledge of concentration-time profiles in both plasma and urine are required. In this study, dexamethasone plasma and urine concentration-time profiles were investigated. Endogenous hydrocortisone plasma concentrations and their relationship to dexamethasone plasma concentrations were also explored. A single dose of dexamethasone-21-isonicotinate suspension (0.03mg/kg) was administered intramuscularly to six horses. Plasma was analysed for dexamethasone and hydrocortisone and urine for dexamethasone, using UPLC-MS/MS. Dexamethasone was quantifiable in plasma for 8.3 +/- 2.9days (LLOQ: 0.025g/L) and in urine for 9.8 +/- 3.1days (LLOQ: 0.15g/L). Maximum observed dexamethasone concentration in plasma was 0.61 +/- 0.12g/L and in urine 4.2 +/- 0.9g/L. Terminal plasma half-life was 38.7 +/- 19h. Hydrocortisone was significantly suppressed for 140h. The plasma half-life of hydrocortisone was 2.7 +/- 1.3h. Dexamethasone potency, efficacy and sigmoidicity factor for hydrocortisone suppression were 0.06 +/- 0.04g/L, 0.95 +/- 0.04 and 6.2 +/- 4.6, respectively. Hydrocortisone suppression relates to the plasma concentration of dexamethasone. Thus, determination of irrelevant plasma concentrations and SL is possible. Future research will determine whether hydrocortisone suppression can be used as a biomarker of the clinical effect of dexamethasone.

  • 93.
    Ekstrand, C.
    et al.
    Swedish Univ Agr Sci, Dept Biomed Sci & Vet Publ Hlth, Div Pharmacol & Toxicol, SE-75007 Uppsala, Sweden..
    Ingvast-Larsson, C.
    Swedish Univ Agr Sci, Dept Biomed Sci & Vet Publ Hlth, Div Pharmacol & Toxicol, SE-75007 Uppsala, Sweden..
    Olsen, L.
    Swedish Univ Agr Sci, Dept Biomed Sci & Vet Publ Hlth, Div Pharmacol & Toxicol, SE-75007 Uppsala, Sweden..
    Hedeland, Mikael
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Analytical Pharmaceutical Chemistry. Natl Vet Inst SVA, Dept Chem Environm & Feed Hyg, Uppsala, Sweden..
    Bondesson, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Analytical Pharmaceutical Chemistry. Natl Vet Inst SVA, Dept Chem Environm & Feed Hyg, Uppsala, Sweden..
    Gabrielsson, J.
    Swedish Univ Agr Sci, Dept Biomed Sci & Vet Publ Hlth, Div Pharmacol & Toxicol, SE-75007 Uppsala, Sweden..
    A quantitative approach to analysing cortisol response in the horse2016In: Journal of Veterinary Pharmacology and Therapeutics, ISSN 0140-7783, E-ISSN 1365-2885, Vol. 39, no 3, p. 255-263Article in journal (Refereed)
    Abstract [en]

    The cortisol response to glucocorticoid intervention has, in spite of several studies in horses, not been fully characterized with regard to the determinants of onset, intensity and duration of response. Therefore, dexamethasone and cortisol response data were collected in a study applying a constant rate infusion regimen of dexamethasone (0.17, 1.7 and 17g/kg) to six Standardbreds. Plasma was analysed for dexamethasone and cortisol concentrations using UHPLC-MS/MS. Dexamethasone displayed linear kinetics within the concentration range studied. A turnover model of oscillatory behaviour accurately mimicked cortisol data. The mean baseline concentration range was 34-57g/L, the fractional turnover rate 0.47-1.5 1/h, the amplitude parameter 6.8-24g/L, the maximum inhibitory capacity 0.77-0.97, the drug potency 6-65ng/L and the sigmoidicity factor 0.7-30. This analysis provided a better understanding of the time course of the cortisol response in horses. This includes baseline variability within and between horses and determinants of the equilibrium concentration-response relationship. The analysis also challenged a protocol for a dexamethasone suppression test design and indicated future improvement to increase the predictability of the test.

  • 94.
    Ekstrand, Carl
    et al.
    Swedish Univ Agr Sci, Fac Vet Med & Anim Sci, Dept Biomed Sci & Vet Publ Hlth, Box 7058, S-75007 Uppsala, Sweden.
    Bondesson, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry. Natl Vet Inst SVA, Dept Chem Environm & Feed Hyg, S-75189 Uppsala, Sweden.
    Giving, Ellen
    Romerike Hesteklin, Riisveien 75, N-2007 Kjeller, Norway.
    Hedeland, Mikael
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry. Natl Vet Inst SVA, Dept Chem Environm & Feed Hyg, S-75189 Uppsala, Sweden.
    Ingvast-Larsson, Carina
    Swedish Univ Agr Sci, Fac Vet Med & Anim Sci, Dept Biomed Sci & Vet Publ Hlth, Box 7058, S-75007 Uppsala, Sweden.
    Jacobsen, Stine
    Univ Copenhagen, Fac Hlth & Med Sci, Dept Vet Clin Sci, Dyrlaevej 16, DK-1870 Frederiksberg C, Denmark.
    Löfgren, Maria
    Swedish Univ Agr Sci, Fac Vet Med & Anim Sci, Dept Biomed Sci & Vet Publ Hlth, Box 7058, S-75007 Uppsala, Sweden.
    Moen, Lars
    Romerike Hesteklin, Riisveien 75, N-2007 Kjeller, Norway.
    Rhodin, Marie
    Swedish Univ Agr Sci, Fac Vet Med & Anim Sci, Dept Anat Physiol & Biochem, Box 7011, S-75007 Uppsala, Sweden.
    Saetra, Tonje
    Rikstotoklinikken Bjerke, Postboks 194, N-0510 Oslo, Norway.
    Ranheim, Birgit
    Norwegian Univ Life Sci, Fac Vet Med, Prod Anim Clin Sci, Box 369 Sentrum, N-0102 Oslo, Norway.
    Disposition and effect of intra-articularly administered dexamethasone on lipopolysaccharide induced equine synovitis2019In: Acta Veterinaria Scandinavica, ISSN 1751-0147, E-ISSN 1751-0147, Vol. 61, article id 28Article in journal (Refereed)
    Abstract [en]

    Background: Dexamethasone is used for the intra-articular route of administration in management of aseptic arthritis in horses. Despite its widespread use there is very little quantitative data of the disposition and response to dexamethasone. The aim of this study was to investigate and describe the synovial fluid and plasma dexamethasone concentration over time and to explore the relation between synovial fluid concentration and response using clinical endpoints as response biomarkers after IA injection of dexamethasone disodium salt solution in an equine model of synovitis.

    Results: Inflammation was induced in the radiocarpal joint of six horses by injection of 2ng lipopolysaccharide (LPS). Two hours later either saline or dexamethasone was injected in the same joint in a two treatment cross over design. Each horse was treated once with one of the six doses dexamethasone used (0.01, 0.03, 0.1, 0.3, 1 or 3mg) and once with saline. Dexamethasone was quantified by means of UHPLC-MS/MS. Dexamethasone disposition was characterised by means of a non-linear mixed effects model. Lameness was evaluated both objectively with an inertial sensor based system and subjectively scored using a numerical scale (0-5). Joint circumference, skin temperature over the joint and rectal temperature were also recorded. The LPS-challenge induced lameness in all horses with high inter-individual variability. Dexamethasone significantly decreased lameness compared with saline. Other variables were not statistically significant different between treatments. Objective lameness scoring was the most sensitive method used in this study to evaluate the lameness response. A pharmacokinetic/pharmacodynamic model was successfully fitted to experimental dexamethasone and lameness data. The model allowed characterization of the dexamethasone synovial fluid concentration-time course, the systemic exposure to dexamethasone after intra-articular administration and the concentration-response relation in an experimental model of synovitis.

    Conclusions: The quantitative data improve the understanding of the pharmacology of dexamethasone and might serve as input for future experiments and possibly contribute to maintain integrity of equine sports.

  • 95.
    Ekstrand, Carl
    et al.
    Swedish Univ Agr Sci, Div Pharmacol & Toxicol, Dept Biomed & Vet Publ Hlth, POB 7028, S-75007 Uppsala, Sweden.
    Ingvast-Larsson, Carina
    Swedish Univ Agr Sci, Div Pharmacol & Toxicol, Dept Biomed & Vet Publ Hlth, POB 7028, S-75007 Uppsala, Sweden.
    Bondesson, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Analytical Pharmaceutical Chemistry. Natl Vet Inst, Dept Chem Environm & Feed Hyg, Uppsala, Sweden.
    Hedeland, Mikael
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Analytical Pharmaceutical Chemistry. Natl Vet Inst, Dept Chem Environm & Feed Hyg, Uppsala, Sweden.
    Olsen, Lena
    Swedish Univ Agr Sci, Div Pharmacol & Toxicol, Dept Biomed & Vet Publ Hlth, POB 7028, S-75007 Uppsala, Sweden;Swedish Univ Agr Sci, Div Vet Nursing, Dept Clin Sci, Uppsala, Sweden.
    Cetirizine per os: exposure and antihistamine effect in the dog2018In: Acta Veterinaria Scandinavica, ISSN 1751-0147, E-ISSN 1751-0147, Vol. 60, article id 77Article in journal (Refereed)
    Abstract [en]

    BackgroundCetirizine is an antihistamine used in dogs, but plasma concentrations in relation to effect after oral administration are not well studied. This study investigated cetirizine exposure and the plasma cetirizine concentration-antihistamine response relation in the dog following oral administration of cetirizine.ResultsEight Beagle dogs were included in a cross-over study consisting of two treatments. In treatment one, cetirizine 2-4mg/kg was administered per os once daily for 3days. The other treatment served as a control. Wheal diameter induced by intra-dermal histamine injections served as response-biomarker. Cetirizine plasma concentration was quantified by UHPLC-MS/MS. Median (range) cetirizine plasma terminal half-life was 10h (7.9-16.5). Cetirizine significantly inhibited wheal formation compared with the premedication baseline. Maximum inhibition of wheal formation after treatment with cetirizine per os was 100% compared with premedication wheal diameter. The median (range) IC50-value for reduction in wheal area was 0.33 mu g/mL (0.07-0.45). The median (range) value for the sigmoidicity factor was 1.8 (0.8-3.5). A behavioral study was also conducted and revealed no adverse effects, such as sedation.ConclusionThe results indicate that a once-daily dosing regimen of 2-4mg/kg cetirizine per os clearly provides a sufficient antihistamine effect. Based on this experimental protocol, cetirizine may be an option to treat histamine-mediated inflammation in the dog based on this experimental protocol but additional clinical studies are required.

  • 96. Ekstrand, Carl
    et al.
    Sterning, Marie
    Bohman, Love
    Stockholm University, Faculty of Social Sciences, Department of Sociology.
    Edner, Anna
    Lumbo-sacral epidural anaesthesia as a complement to dissociative anaesthesia during scrotal herniorrhaphy of livestock pigs in the field2015In: Acta Veterinaria Scandinavica, ISSN 0044-605X, Vol. 57, article id 33Article in journal (Refereed)
    Abstract [en]

    Background: In Sweden, scrotal or inguinal herniorrhaphy of livestock pigs in the field has traditionally been an important part of the surgical skills training of veterinary students. Few substances meet the legal requirements for field anaesthesia of production animals in the European Union but a protocol based on azaperone-detomidine-butorphanol-ketamine does. Unfortunately the anaesthesia is characterised by unpredictable duration and depth and of abrupt awakenings which is not acceptable from an animal welfare perspective and impedes surgical training. Lumbo-sacral epidural analgesia is proven to provide sufficient analgesia to allow abdominal surgery, but there are few reports on the field use of this loco-regional technique. The study aim was to evaluate whether lumbo-sacral anaesthesia can be safely and successfully used in the field by a veterinary student and whether the combination of dissociative and lumbo-sacral epidural anaesthesia improves analgesia and anaesthesia to guarantee animal welfare during herniorrhaphy in livestock pigs, enabling surgical skills training. Results: Pigs in the control-group (placebo) responded significantly stronger to surgery, with five out of 11 requiring additional doses of detomidine and ketamine. There were no significant differences between groups in respiratory rate, heart rate, blood pressure, SpO(2) or blood gases. SpO(2) levels <94 % were recorded in several pigs in both groups. No post-injection complications were reported at follow-up. Conclusions: The results from this study showed that lumbo-sacral epidural anaesthesia with lidocaine could successfully be administered during dissociative anaesthesia of livestock pigs by a veterinary student and without reported post-injection complications. It improved analgesia and anaesthesia during herniorrhaphy of sufficient duration to enable surgical skills training. The risks and consequences of hypoxaemia and hypoventilation should be considered.

  • 97.
    Ekström, Anette
    et al.
    University of Skövde, School of Life Sciences.
    Nissen, Eva
    University of Skövde, School of Life Sciences.
    Process-oriented training in breastfeeding attitudes and continuity of care improve mothers perception of support2007In: Health Education Research Trends / [ed] Peter R. Hong, Nova Science Publishers, Inc., 2007, p. 211-225Chapter in book (Refereed)
  • 98.
    Eld, Karin
    et al.
    Bacteriological Laboratory, National Veterinary Institute, Uppsala, Sweden.
    Danielsson Tham, Marie-Louise
    Department of Food Hygiene, Faculty of Veterinary Medicine, Swedish University of Agricultural Sciences, Uppsala, Sweden.
    Gunnarsson, Anders
    Bacteriological Laboratory, National Veterinary Institute, Uppsala, Sweden.
    Tham, Wilhelm
    Department of Food Hygiene, Faculty of Veterinary Medicine, Swedish University of Agricultural Sciences, Uppsala, Sweden.
    Comparison of a cold enrichment method and the IDF method for isolation of Listeria monocytogenes from animal autopsy material1992In: Listeria 1992: The Eleventh International Symposium on Problems of Listeriosis: book of abstracts, København: Statens Seruminstitut , 1992, p. 158-159Conference paper (Refereed)
  • 99.
    Eld, Karin
    et al.
    Bacteriological Laboratory, National Veterinary Institute, Uppsala, Sweden.
    Danielsson Tham, Marie-Louise
    Department of Food Hygiene, Faculty of Veterinary Medicine, Swedish University of Agricultural Sciences, Uppsala, Sweden.
    Gunnarsson, Anders
    Bacteriological Laboratory, National Veterinary Institute, Uppsala, Sweden.
    Tham, Wilhelm
    Department of Food Hygiene, Faculty of Veterinary Medicine, Swedish University of Agricultural Sciences, Uppsala, Sweden.
    Comparison of a cold enrichment method and the IDF method for isolation of Listeria monocytogenes from autopsy material1993In: Veterinary Microbiology, ISSN 0378-1135, E-ISSN 1873-2542, Vol. 36, no 1-2, p. 185-189Article in journal (Refereed)
    Abstract [en]

    The method most often used in Sweden for isolation of Listeria monocytogenes from animal autopsy material is a cold enrichment method. This method is very slow. The International Dairy Federation (IDF) has recently presented a method for detection of L. monocytogenes in milk and milk products that is complete in one week. During a two year period 69 specimens from dead animals with suspected listeriosis were examined for L. monocytogenes in parallel analyses with both the cold enrichment method and the IDF method. Samples derived from different autopsy material representing a variety of animals. L. monocytogenes was isolated in 27.5% of the samples with the IDF method but only in 4.3% with the cold enrichment method. It is concluded that the IDF method was more sensitive than the cold enrichment method.

  • 100.
    Elffors, Jenny
    et al.
    Södertörn University College, School of Business Studies.
    Johannessen, Athena
    Södertörn University College, School of Business Studies.
    Marknadsföring på recept: Läkemedelsmarknadsföring ur ett moraliskt perspektiv2008Independent thesis Basic level (degree of Bachelor), 10 points / 15 hpStudent thesis
    Abstract [en]

    Aims: Overall aims of this thesis are to bring a broader and deeper understanding, from  a moral point of view, of marketing of pharmaceuticals, and to consider whether  there is a reason for separating advertising from information in the sector.

    Methods: A qualitative approach to the subject was used. Methods for data compilation  were semi-structured interviews with representatives for The Swedish Association  of the Pharmaceutical Industry (Läkemedelsindustriföreningen), and studies  of advertisements in The Journal of the Swedish Medical Association (Läkartidningen)  and commercials on a TV channel (TV4). A customised, self-made,  grid was utilised for coding and compiling data from the observations of commercial  material. Following that, the empirical material from interviews as well  as observations has been analysed, using the theory of counter productivity as a  model for ethical audit.

    Results: The authors judge marketing activities of the pharmaceutical industry to be morally  justified. One reason for this judgement is, that the pharmaceutical industry  contributes to an increased well-being among citizens by providing research, research  activities being financed by revenues, which – in turn – are enhanced by  marketing. Another reason is that companies show responsible in the dissemination  of information and that the results of the study indicate sincerity in marketing.  When responsibility is linked to trustworthiness and when availability of information  provided by marketing activities is taken into consideration, there is  also evidence of a morally justifiable behaviour. Advertisements for drugs on  prescription showed more informatively designed than those for over-the-counter  drugs. A more informative and appropriate marketing of non-prescription pharmaceuticals  would enhance the moral reputation of the companies.

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