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  • 1.
    Ahlgren, Kerstin, M.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Wilbe, Maria
    Sundberg, Katarina
    Eloranta, Maija-Leena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Lindblad-Toh, Kerstin
    Andersson, Göran
    Lobell, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Hansson-Hamlin, Helene
    Kämpe, Olle
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Type I Interferon signature in Nova Scotia duck tolling retriever dogs with steroid responsive meningitis-arteritisManuscript (preprint) (Other academic)
    Abstract [en]

    Objective: Dogs of the breed Nova Scotia duck tolling retriever (NSDTR) are prone to develop a disease complex in some aspects resembling human systemic lupus erythematosus (SLE). Peripheral blood mononuclear cells (PBMCs) from human SLE patients have an increased mRNA expression type I interferon (IFN) regulated genes. However, it is unknown whether diseased dogs also display the typical type I IFN signature.

    Methods: To test canine sera for their capacity to induce type I IFN response Mardin-Darby canine kidney (MDCK) cells were cultured with sera from healthy dogs (n=25),  immune-mediated rheumatic disease (IMRD) dogs with anti-nuclear antibodies (ANA+) (n=30) or dogs with steroid responsive meningitis-arteritis (SRMA) (n=25). mRNA expression of the genes MX1, IFIT1 and CXCL10 was measured by quantitative Real Time PCR.

    Results: A highly significant (p=0.0009) increase in mRNA expression of the type I IFN responsive gene MX1 was detected in cells stimulated by sera from dogs with SRMA, but not from IMRD ANA+ dogs. Expression of IFIT1 was twice as high in cells stimulated by sera from dogs with SRMA compared to both healthy dogs and ANA+ dogs. The mean expression of CXCL10 was nearly ten times higher in cells stimulated by sera from SRMA dogs than by ANA+ dogs and four times higher compared to cells stimulated by control dogs.

    Conclusion: Presence of type I IFN in sera from diseased NSDTR dogs was found in this study. This implies that this canine model can be used for identification of pathways of importance for autoimmune disorders in humans and for testing of novel therapeutic approaches. Our results can also be a step on the way towards personalized drugs in these dogs.

  • 2. Ahsan, Murshidul
    et al.
    Hasan, Badrul
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology and Infectious Medicine.
    Algotsson, Magnus
    Sarenbo, Sirkku
    Handling and Welfare of Bovine Livestock at Local Abattoirs in Bangladesh2014In: Journal of Applied Animal Welfare Science, ISSN 1088-8705, E-ISSN 1532-7604, Vol. 17, no 4, p. 340-353Article in journal (Refereed)
    Abstract [en]

    The World Organization for Animal Health (OIE) allows rope casting and the tying of legs for nonhuman animals laughter without stunning. The handling and welfare of bovine livestock (Bosindicus and Bubalus bubalis) were studied in 8 local abattoirs in 5 districts of Bangladesh. A total of 302 animals were evaluated. At the local abattoirs, approximately 1/3 of the cattle and water buffalo were eithere maciated orinjured/sick. The size and vigor of the animals determined the casting method. Small and weak animals were cast on concrete floors by lifting a foreleg followed by pushing, or simply by twisting the head of the animal and then binding the legs with rope. Vigorous animals such as buffalo were castusing ropes and human force. Bleeding was slow and flaying was sometimes initiated before the animals were unconscious. Pulling and tearing of the trachea and pouring of water into the exposed trache a shortly after cutting were also observed in some cases.The over all animal handling was unnecessarily rough and he OIE standards were not implemented. Animals are subjected to considerable mistreatment, and there is an urgent need for the training nde ducation of the staff in a battoirs concerning humanes laughtering practices as well as a need to build moderns laughtering plants in Bangladesh.

  • 3.
    Ardesjö-Lundgren, Brita
    et al.
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Swedish Univ Agr Sci, Dept Anim Breeding & Genet, Box 7023, SE-75007 Uppsala, Sweden..
    Tengvall, Katarina
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Karolinska Inst, Neuroimmunol Unit, Centrum Mol Med, Dept Clin Neurosci, S-17176 Stockholm, Sweden..
    Bergvall, Kerstin
    Swedish Univ Agr Sci, Dept Clin Sci, Box 7054, SE-75007 Uppsala, Sweden..
    Farias, Fabiana H. G.
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Wang, Liya
    Swedish Univ Agr Sci, Dept Anat Physiol & Biochem, Box 7011, S-75007 Uppsala, Sweden..
    Hedhammar, Åke
    Swedish Univ Agr Sci, Dept Clin Sci, Box 7054, SE-75007 Uppsala, Sweden..
    Lindblad-Toh, Kerstin
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Broad Inst MIT & Harvard, 415 Main St, Cambridge, MA 02142 USA..
    Andersson, Göran
    Swedish Univ Agr Sci, Dept Anim Breeding & Genet, Box 7023, SE-75007 Uppsala, Sweden..
    Comparison of cellular location and expression of Plakophilin-2 in epidermal cells from nonlesional atopic skin and healthy skin in German shepherd dogs2017In: Veterinary dermatology (Print), ISSN 0959-4493, E-ISSN 1365-3164, Vol. 28, no 4, p. 377-e88Article in journal (Refereed)
    Abstract [en]

    Background - Canine atopic dermatitis (CAD) is an inflammatory and pruritic allergic skin disease caused by interactions between genetic and environmental factors. Previously, a genome-wide significant risk locus on canine chromosome 27 for CAD was identified in German shepherd dogs (GSDs) and Plakophilin-2 (PKP2) was defined as the top candidate gene. PKP2 constitutes a crucial component of desmosomes and also is important in signalling, metabolic and transcriptional activities.

    Objectives - The main objective was to evaluate the role of PKP2 in CAD by investigating PKP2 expression and desmosome structure in nonlesional skin from CAD-affected (carrying the top GWAS SNP risk allele) and healthy GSDs. We also aimed at defining the cell types in the skin that express PKP2 and its intracellular location.

    Animals/Methods - Skin biopsies were collected from nine CAD-affected and five control GSDs. The biopsies were frozen for immunofluorescence and fixed for electron microscopy immunolabelling and morphology.

    Results - We observed the novel finding of PKP2 expression in dendritic cells and T cells in dog skin. Moreover, we detected that PKP2 was more evenly expressed within keratinocytes compared to its desmosomal binding partner plakoglobin. PKP2 protein was located in the nucleus and on keratin filaments attached to desmosomes. No difference in PKP2 abundance between CAD cases and controls was observed.

    Conclusion - Plakophilin-2 protein in dog skin is expressed in both epithelial and immune cells; based on Its sub cellular location its functional role is implicated in both nuclear and structural processes.

  • 4.
    Beasley, Val Richard
    et al.
    University of Illinois at Urbana-Champaign,.
    Adkesson, Adriane Michelle
    University of Illinois at Urbana-Champaign,.
    1. Wildlife and Ecosystem Health2012In: Ecology and Animal Health / [ed] Leif Norrgren and Jeffrey Levengood, Uppsala: Baltic University Press , 2012, 1, p. 13-26Chapter in book (Other (popular science, discussion, etc.))
  • 5.
    Berg, Frida
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Gustafson, Ulla
    Andersson, Leif
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    The uncoupling protein 1 gene (UCP1) is disrupted in the pig lineage: A genetic explanation for poor thermoregulation in piglets2006In: PLoS Genetics, ISSN 1553-7390, Vol. 2, no 8, p. 1178-1181Article in journal (Refereed)
    Abstract [en]

    Piglets appear to lack brown adipose tissue, a specific type of fat that is essential for nonshivering thermogenesis in mammals, and they rely on shivering as the main mechanism for thermoregulation. Here we provide a genetic explanation for the poor thermoregulation in pigs as we demonstrate that the gene for uncoupling protein 1 (UCP1) was disrupted in the pig lineage. UCP1 is exclusively expressed in brown adipose tissue and plays a crucial role for thermogenesis by uncoupling oxidative phosphorylation. We used long-range PCR and genome walking to determine the complete genome sequence of pig UCP1. An alignment with human UCP1 revealed that exons 3 to 5 were eliminated by a deletion in the pig sequence. The presence of this deletion was confirmed in all tested domestic pigs, as well as in European wild boars, Bornean bearded pigs, wart hogs, and red river hogs. Three additional disrupting mutations were detected in the remaining exons. Furthermore, the rate of nonsynonymous substitutions was clearly elevated in the pig sequence compared with the corresponding sequences in humans, cattle, and mice, and we used this increased rate to estimate that UCP1 was disrupted about 20 million years ago.

  • 6.
    Berglund, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Separation of Water and Fat Signal in Magnetic Resonance Imaging: Advances in Methods Based on Chemical Shift2011Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Magnetic resonance imaging (MRI) is one of the most important diagnostic tools of modern healthcare. The signal in medical MRI predominantly originates from water and fat molecules. Separation of the two components into water-only and fat-only images can improve diagnosis, and is the premier non-invasive method for measuring the amount and distribution of fatty tissue.

    Fat-water imaging (FWI) enables fast fat/water separation by model-based estimation from chemical shift encoded data, such as multi-echo acquisitions. Qualitative FWI is sufficient for visual separation of the components, while quantitative FWI also offers reliable estimates of the fat percentage in each pixel. The major problems of current FWI methods are long acquisition times, long reconstruction times, and reconstruction errors that degrade image quality.

    In this thesis, existing FWI methods were reviewed, and novel fully automatic methods were developed and evaluated, with a focus on fast 3D image reconstruction. All MRI data was acquired on standard clinical scanners.

    A triple-echo qualitative FWI method was developed for the specific application of 3D whole-body imaging. The method was compared with two reference methods, and demonstrated superior image quality when evaluated in 39 volunteers.

    The problem of qualitative FWI by dual-echo data with unconstrained echo times was solved, allowing faster and more flexible image acquisition than conventional FWI. Feasibility of the method was demonstrated in three volunteers and the noise performance was evaluated.

    Further, a quantitative multi-echo FWI method was developed. The signal separation was based on discrete whole-image optimization. Fast 3D image reconstruction with few reconstruction errors was demonstrated by abdominal imaging of ten volunteers.

    Lastly, a method was proposed for quantitative mapping of average fatty acid chain length and degree of saturation. The method was validated by imaging different oils, using gas-liquid chromatography (GLC) as the reference. The degree of saturation agreed well with GLC, and feasibility of the method was demonstrated in the thigh of a volunteer.

    The developed methods have applications in clinical settings, and are already being used in several research projects, including studies of obesity, dietary intervention, and the metabolic syndrome.

    List of papers
    1. Three-point Dixon method enables whole-body water and fat imaging of obese subjects
    Open this publication in new window or tab >>Three-point Dixon method enables whole-body water and fat imaging of obese subjects
    2010 (English)In: Magnetic Resonance in Medicine, ISSN 0740-3194, E-ISSN 1522-2594, Vol. 63, no 6, p. 1659-1668Article in journal (Refereed) Published
    Abstract [en]

    Dixon imaging techniques derive chemical shift-separated water and fat images, enabling the quantification of fat content and forming an alternative to fat suppression. Whole-body Dixon imaging is of interest in studies of obesity and the metabolic syndrome, and possibly in oncology. A three-point Dixon method is proposed where two solutions are found analytically in each voxel. The true solution is identified by a multiseed three-dimensional region-growing scheme with a dynamic path, allowing confident regions to be solved before unconfident regions, such as background noise. 2 pi-Phase unwrapping is not required. Whole-body datasets (256 x 184 x 252 voxels) were collected from 39 subjects (body mass index 19.8-45.4 kg/m(2)), in a mean scan time of 5 min 15 sec. Water and fat images were reconstructed offline, using the proposed method and two reference methods. The resulting images were subjectively graded on a four-grade scale by two radiologists, blinded to the method used. The proposed method was found superior to the reference methods. It exclusively received the two highest grades, implying that only mild reconstruction failures were found. The computation time for a whole-body dataset was 1 min 51.5 sec +/- 3.0 sec. It was concluded that whole-body water and fat imaging is feasible even for obese subjects, using the proposed method.

    Keywords
    three-point Dixon, whole-body MRI, water and fat separation, chemical shift imaging, fat suppression
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:uu:diva-129498 (URN)10.1002/mrm.22385 (DOI)000278164400026 ()20512869 (PubMedID)
    Available from: 2010-08-17 Created: 2010-08-17 Last updated: 2017-12-12Bibliographically approved
    2. Two-point dixon method with flexible echo times
    Open this publication in new window or tab >>Two-point dixon method with flexible echo times
    2011 (English)In: Magnetic Resonance in Medicine, ISSN 0740-3194, E-ISSN 1522-2594, Vol. 65, no 4, p. 994-1004Article in journal (Refereed) Published
    Abstract [en]

    The two-point Dixon method is a proton chemical shift imaging technique that produces separated water-only and fat-only images from a dual-echo acquisition. It is shown how this can be achieved without the usual constraints on the echo times. A signal model considering spectral broadening of the fat peak is proposed for improved water/fat separation. Phase errors, mostly due to static field inhomogeneity, must be removed prior to least-squares estimation of water and fat. To resolve ambiguity of the phase errors, a corresponding global optimization problem is formulated and solved using a message-passing algorithm. It is shown that the noise in the water and fat estimates matches the Cramér-Rao bounds, and feasibility is demonstrated for in vivo abdominal breath-hold imaging. The water-only images were found to offer superior fat suppression compared with conventional spectrally fat suppressed images.

    Keywords
    chemical shift imaging, fat suppression, two-point Dixon, water and fat separation
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:uu:diva-150936 (URN)10.1002/mrm.22679 (DOI)000288612000011 ()21413063 (PubMedID)
    Available from: 2011-04-08 Created: 2011-04-08 Last updated: 2017-12-11Bibliographically approved
    3. Three-dimensional water/fat separation and T2* estimation based on whole-image optimization: application in breathhold liver imaging at 1.5 T
    Open this publication in new window or tab >>Three-dimensional water/fat separation and T2* estimation based on whole-image optimization: application in breathhold liver imaging at 1.5 T
    2012 (English)In: Magnetic Resonance in Medicine, ISSN 0740-3194, E-ISSN 1522-2594, Vol. 67, no 6, p. 1684-1693Article in journal (Refereed) Published
    Abstract [en]

    The chemical shift of water and fat resonances in proton MRI allows separation of water and fat signal from chemical shift encoded data. This work describes an automatic method that produces separate water and fat images as well as quantitative maps of fat signal fraction and T2* from complex multi-echo gradient recalled datasets. Accurate water and fat separation is challenging due to signal ambiguity at the voxel level. Whole-image optimization can resolve this ambiguity, but might be computationally demanding, especially for three-dimensional (3D) data. In this work, periodicity of the model fit residual as a function of the off-resonance was utilized to modify a previously proposed formulation of the problem. This gives a smaller solution space and allows rapid optimization. Feasibility and accurate separation of water and fat signal was demonstrated in breathhold 3D liver imaging of ten volunteer subjects, with both acquisition and reconstruction times below 20 seconds.

    Keywords
    water and fat separation, chemical shift imaging, quantitative MRI, liver fat, T2* mapping, QPBO
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:uu:diva-158097 (URN)10.1002/mrm.23185 (DOI)000304086000020 ()22189760 (PubMedID)
    Available from: 2011-08-31 Created: 2011-08-31 Last updated: 2017-12-08Bibliographically approved
    4. Model-based mapping of fat unsaturation and chain length by chemical shift imaging: phantom validation and in vivo feasibility
    Open this publication in new window or tab >>Model-based mapping of fat unsaturation and chain length by chemical shift imaging: phantom validation and in vivo feasibility
    2012 (English)In: Magnetic Resonance in Medicine, ISSN 0740-3194, E-ISSN 1522-2594, Vol. 68, no 6, p. 1815-1827Article in journal (Refereed) Published
    Abstract [en]

    Knowledge about the triglyceride (fat) 1H spectrum enables quantitative determination of several triglyceride characteristics. This work describes a model-based chemical shift imaging method that separates water and fat signal and provides maps of three triglyceride quantities: fatty acid carbon chain length (CL), number of double bond pairs (ndb), and number of methylene-interrupted double bonds (nmidb). The method was validated by imaging a phantom containing ten different oils using 1.5 T and 3.0 T clinical scanners, with gas-liquid chromatography (GLC) as reference. Repeated acquisitions demonstrated high reproducibility of the method. Statistical tests of correlation and linear regression were performed to examine the accuracy of the method. Significant correlation was found at both field strengths for all three quantities, and high correlation (r2 > 0.96) was found for measuring ndb and nmidb. Feasibility of the method for in vivo imaging of the thigh was demonstrated at both field strengths. The estimates of ndb and nmidb in subcutaneous adipose tisse were in agreement with literature values, while CL appears overestimated. The method has potential use in large-scale cross-sectional and longitudinal studies of triglyceride composition, and its relation to diet and various diseases.

    Keywords
    water/fat separation, chemical shift imaging, quantitative MRI, fat unsaturation, triglyceride mapping, fatty acid composition
    National Category
    Radiology, Nuclear Medicine and Medical Imaging
    Identifiers
    urn:nbn:se:uu:diva-158098 (URN)10.1002/mrm.24196 (DOI)000311398600015 ()22334300 (PubMedID)
    Available from: 2011-08-31 Created: 2011-08-31 Last updated: 2017-12-08Bibliographically approved
  • 7.
    Bergman, Daniel
    et al.
    Department of Clinical Sciences, Swedish University of Agricultural Sciences, Uppsala, Sweden..
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Hansson-Hamlin, Helene
    Department of Clinical Sciences, Swedish University of Agricultural Sciences, Uppsala, Sweden..
    Svensson, Anna
    Department of Clinical Sciences, Swedish University of Agricultural Sciences, Uppsala, Sweden..
    Holst, Bodil Ström
    Department of Clinical Sciences, Swedish University of Agricultural Sciences, Uppsala, Sweden..
    Prevalence of interfering antibodies in dogs and cats evaluated using a species-independent assay.2018In: Veterinary clinical pathology, ISSN 0275-6382, E-ISSN 1939-165X, Vol. 47, no 2, p. 205-212Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Interfering antibodies in human serum and plasma are known to react with mammalian antibodies in immunoassays and cause false-positive test results. Although this phenomenon was recently shown in companion animals, knowledge regarding immunoassay interference in veterinary medicine is very limited.

    OBJECTIVES: The aims of this study were to set up a species-independent immunoassay procedure to detect interference in serum samples, to screen for interference in a cross-section of canine and feline patient samples from an animal hospital, and to determine if the detected interference could be neutralized using an immunoassay based on nonmammalian reagents.

    METHODS: A 2-site sandwich-type interference assay was set up using commercially available mouse reagents. A total of 369 serum samples from 320 dogs and 263 samples from 218 cats were analyzed using the interference assay. Multiple samples were submitted from 36 dogs and 39 cats. Nineteen samples identified as interference-positive were analyzed in an assay using chicken antibodies.

    RESULTS: Interference was detected in samples from 28 dogs (9%) and 10 cats (5%) screened with the interference assay. Except for 1 cat, consistent results were obtained for all 75 dogs and cats that submitted more than 1 sample. The interference was eliminated when analyzed in the chicken-based assay (P < .001).

    CONCLUSIONS: Substances with reactivity toward mouse IgG can be detected in serum samples from dog and cat patients using a 2-site interference assay. The detected substances are most likely interfering antibodies, possibly originating from immunization with other mammalian species.

  • 8.
    Betsholtz, Christer
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Cancer and Vascular Biology.
    Keller, Annika
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Cancer and Vascular Biology.
    PDGF, Pericytes and the Pathogenesis of Idiopathic Basal Ganglia Calcification (IBGC)2014In: Brain Pathology, ISSN 1015-6305, E-ISSN 1750-3639, Vol. 24, no 4, p. 387-395Article in journal (Refereed)
    Abstract [en]

    Platelet-derived growth factors (PDGFs) are important mitogens for various types of mesenchymal cells, and as such, they exert critical functions during organogenesis in mammalian embryonic and early postnatal development. Increased or ectopic PDGF activity may also cause or contribute to diseases such as cancer and tissue fibrosis. Until recently, no loss-of-function (LOF) mutations in PDGF or PDGF receptor genes were reported as causally linked to a human disease. This changed in 2013 when reports appeared on presumed LOF mutations in the genes encoding PDGF-B and its receptor PDGF receptor-beta (PDGF-R) in familial idiopathic basal ganglia calcification (IBGC), a brain disease characterized by anatomically localized calcifications in or near the blood microvessels. Here, we review PDGF-B and PDGF-R biology with special reference to their functions in brain-blood vessel development, pericyte recruitment and the regulation of the blood-brain barrier. We also discuss various scenarios for IBGC pathogenesis suggested by observations in patients and genetically engineered animal models of the disease.

  • 9.
    Bignert, Anders
    et al.
    Swedish Museum of Natural History, Stockholm, Sweden.
    Bäcklin, Britt-Marie
    Swedish Museum of Natural History, Stockholm, Sweden.
    Helander, Björn
    Swedish Museum of Natural History, Stockholm, Sweden.
    Roos, Anna
    Swedish Museum of Natural History, Stockholm, Sweden.
    9. Contaminants and Health of Aquatic Wildlife2012In: Ecology and Animal Health / [ed] Leif Norrgren and Jeffrey Levengood, Uppsala: Baltic University Press , 2012, 1, p. 73-85Chapter in book (Other (popular science, discussion, etc.))
  • 10. Breed, Andrew C.
    et al.
    Breed, Martin F.
    Australian Centre for Evolutionary Biology and Biodiversity (ACEBB), and School of Earth and Environmental Sciences, University of Adelaide.
    Meers, Joanne
    Field, Hume E.
    Evidence of endemic Hendra virus infection in flying-foxes (Pteropus conspicillatus): implications for disease risk management2011In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 6, p. e28816-Article in journal (Refereed)
    Abstract [en]

    This study investigated the seroepidemiology of Hendra virus in a spectacled flying-fox (Pteropus conspicillatus) population in northern Australia, near the location of an equine and associated human Hendra virus infection in late 2004. The pattern of infection in the population was investigated using a serial cross-sectional serological study over a 25-month period, with blood sampled from 521 individuals over six sampling sessions. Antibody titres to the virus were determined by virus neutralisation test. In contrast to the expected episodic infection pattern, we observed that seroprevalence gradually increased over the two years suggesting infection was endemic in the population over the study period. Our results suggested age, pregnancy and lactation were significant risk factors for a detectable neutralizing antibody response. Antibody titres were significantly higher in females than males, with the highest titres occurring in pregnant animals. Temporal variation in antibody titres suggests that herd immunity to the virus may wax and wane on a seasonal basis. These findings support an endemic infection pattern of henipaviruses in bat populations suggesting their infection dynamics may differ significantly from the acute, self limiting episodic pattern observed with related viruses (e.g. measles virus, phocine distemper virus, rinderpest virus) hence requiring a much smaller critical host population size to sustain the virus. These findings help inform predictive modelling of henipavirus infection in bat populations, and indicate that the life cycle of the reservoir species should be taken into account when developing risk management strategies for henipaviruses.

  • 11.
    Bremer, Hanna D.
    et al.
    Swedish Univ Agr Sci SLU, Dept Clin Sci, Box 7054, SE-75007 Uppsala, Sweden..
    Lattwein, Erik
    Euroimmun AG, Lubeck, Germany..
    Renneker, Stefanie
    Euroimmun AG, Lubeck, Germany..
    Lilliehook, Inger
    Swedish Univ Agr Sci, Univ Anim Hosp, Clin Pathol Lab, Uppsala, Sweden..
    Rönnelid, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Hansson-Hamlin, Helene
    Swedish Univ Agr Sci SLU, Dept Clin Sci, Box 7054, SE-75007 Uppsala, Sweden..
    Identification of specific antinuclear antibodies in dogs using a line immunoassay and enzyme-linked immunosorbent assay2015In: Veterinary Immunology and Immunopathology, ISSN 0165-2427, E-ISSN 1873-2534, Vol. 168, no 3-4, p. 233-241Article in journal (Refereed)
    Abstract [en]

    Circulating antinuclear antibodies (ANA) are commonly present in the systemic autoimmune disease Systemic Lupus Erythematosus (SLE) and in other systemic rheumatic diseases, in humans as well as in dogs. The indirect immunofluorescence (IIF)-ANA test is the standard method for detecting ANA. Further testing for specific ANA with immunoblot techniques or ELISAs is routinely performed in humans to aid in the diagnosis and monitoring of disease. Several specific ANA identified in humans have been identified also in suspected canine SLE but, in contrast to humans, investigation of autoantibodies in canine SLE is mainly restricted to the IIF-ANA test. Our aim was to identify both known and novel specific ANA in dogs and to investigate if different IIF-ANA patterns are associated with different specific ANA in dogs. Sera from 240 dogs with suspicion of autoimmune disease (210 IIF-ANA positive (ANA(pos)) and 30 IIF-ANA negative (ANA(neg))) as well as sera from 27 healthy controls were included. The samples were analysed with a line immunoassay, LIA (Euroline ANA Profile 5, Euroimmun, Lubeck, Germany) and four different ELISAs (Euroimmun). The ANA(pos) dogs were divided in two groups depending on the type of IIF-ANA pattern. Of the 210 ANA(pos) samples 68 were classified as ANA homogenous (ANA(H)) and 141 as ANA speckled (ANA(S)), one sample was not possible to classify. Dogs in the ANA(H) group had, compared to the other groups, most frequently high levels of anti-double stranded deoxyribonucleic acid (dsDNA) and anti-nucleosome ANA. Anti-dsDNA antibodies were confirmed in some dogs with the Crithidia luciliae indirect immunofluorescence test (CLIFT).The frequency of ANA(H) dogs with values above those observed in the healthy group was significantly higher compared to ANA(S) dogs for anti-dsDNA, anti-nucleosome, and anti-histone reactivity. Dogs in the ANA(S) group had, compared to the other groups, most frequently high levels of anti-ribonucleoproteins (RNP) and/or anti-Smith (Sm) antibodies. Reactivity against Sjogren's syndrome related antigens (SS)-A (including the Ro-60 and Ro-52 subcomponents), SS-B, histidyl tRNA synthetase (Jo-1), topoisomerase I antigen (Scl-70), polymyositis-scleroderma antigen (PM-Scl) and proliferating cell nuclear antigen (PCNA) was also noted in individual dogs. In conclusion, by using a commercial LIA and different ELISAs originally developed for detection of human ANA, we identified several specific ANA in serum samples from dogs sampled for IIF-ANA testing. Further, we found that the types of IIF-ANA pattern were associated with reactivity against some particular nuclear antigens.

  • 12. Bröjer, Caroline
    et al.
    Järhult, Josef D.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases.
    Muradrasoli, Shaman
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Virology.
    Söderström, Hanna
    Olsen, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases.
    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 high-pathogenic avian influenza (HPAI) viruses or form part of human-adapted strains with pandemic potential. However, the LPAI infection as such is not very well characterized in the natural reservoir, dabbling ducks, and results are in part contradictory. The effects on the infection by artificial versus natural infection, exposure to antiviral drugs or development of resistance have not been studied. Therefore, we used q-PCR, histopathology and immunohistochemistry (IHC) to study mallards infected with an influenza A/H1N1 virus isolated from a wild mallard in Sweden. The mallards were either inoculated intra-esophageally or infected by virus shed by other ducks in the experiment. The birds were subjected to low levels of the active metabolite of oseltamivir (Tamiflu®) and the resistance mutation H274Y developed during the course of the experiment.

    All mallards but one had a strictly intestinal localization of the LPAI infection. The exception was a bird euthanized one day post artificial inoculation whose infection was located solely in the lung, possibly due to intra-tracheal deposition of virus. The intestinal infection was characterized by degenerating cells in the lamina propria, infiltrating heterophils and lymphocytes as well as positivity of IHC and q-PCR on samples from feces and intestinal contents. Histopathological changes, IHC positivity and viral shedding all indicate that the infection peaked early, around two days post infection. Furthermore, the infection had a longitudinal progression in the intestine with more activity in the proximal parts early in the infection and vice versa as observed both by IHC and by q-PCR. There was no obvious difference in the course of the infection in artificial versus natural infection, when the level of OC was increased from 80 ng/L to 80 µg/L or when the resistance mutation H274Y developed.

  • 13.
    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.

    List of papers
    1.
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    5. Suppressor of cytokine signalling-3 expression inhibits cytokine-mediated destruction of primary mouse and rat pancreatic islets and delays allograft rejection
    Open this publication in new window or tab >>Suppressor of cytokine signalling-3 expression inhibits cytokine-mediated destruction of primary mouse and rat pancreatic islets and delays allograft rejection
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    2008 (English)In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 51, no 10, p. 1873-1882Article in journal (Refereed) Published
    Abstract [en]

    Aims/hypothesis The pro-inflammatory cytokines IL-1 and IFN gamma are critical molecules in immune-mediated beta cell destruction leading to type 1 diabetes mellitus. Suppressor of cytokine signalling (SOCS)-3 inhibits the cytokine-mediated destruction of insulinoma-1 cells. Here we investigate the effect of SOCS3 in primary rodent beta cells and diabetic animal models. Methods Using mice with beta cell-specific Socs3 expression and a Socs3-encoding adenovirus construct, we characterised the protective effect of SOCS3 in mouse and rat islets subjected to cytokine stimulation. In transplantation studies of NOD mice and alloxan-treated mice the survival of Socs3 transgenic islets was investigated. Results Socs3 transgenic islets showed significant resistance to cytokine-induced apoptosis and impaired insulin release. Neither glucose-stimulated insulin release, insulin content or glucose oxidation were affected by SOCS3. Rat islet cultures transduced with Socs3-adenovirus displayed reduced cytokine-induced nitric oxide and apoptosis associated with inhibition of the IL-1-induced nuclear factor-kappa B and mitogen-activated protein kinase (MAPK) pathways. Transplanted Socs3 transgenic islets were not protected in diabetic NOD mice, but showed a prolonged graft survival when transplanted into diabetic allogenic BALB/c mice. Conclusions/interpretation SOCS3 inhibits IL-1-induced signalling through the nuclear factor-kappa B and MAPK pathways and apoptosis induced by cytokines in primary beta cells. Moreover, Socs3 transgenic islets are protected in an allogenic transplantation model. SOCS3 may represent a target for pharmacological or genetic engineering in islet transplantation for treatment of type 1 diabetes mellitus.

    Keywords
    apoptosis, autoimmunity, diabetes, IFN gamma, IL-1, inflammation; signalling, SOCS, suppressor of cytokine signalling
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:uu:diva-97610 (URN)10.1007/s00125-008-1090-0 (DOI)000258958400017 ()
    Available from: 2008-10-10 Created: 2008-10-10 Last updated: 2017-12-14Bibliographically approved
  • 14.
    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. 

  • 15.
    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.

  • 16.
    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.))
  • 17.
    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.

  • 18.
    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.

    List of papers
    1. Effects of ageing and gender on contractile properties in human skeletal muscle and single fibres
    Open this publication in new window or tab >>Effects of ageing and gender on contractile properties in human skeletal muscle and single fibres
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    2007 (English)In: Acta Physiologica, ISSN 1748-1708, E-ISSN 1748-1716, Vol. 190, no 3, p. 229-241Article in journal (Refereed) Published
    Abstract [en]

    Aim: The objective of this study is to improve our understanding of the mechanisms underlying the ageing- and gender-related muscle weakness.

    Methods: Ageing- and gender-related differences in regulation of muscle contraction have been studied in knee-extensor muscles at the whole muscle and single muscle fibre levels in young and old sedentary men and women. In vivo knee-extensor muscle function was measured at slow (30° s−1) and faster (180 ° s−1) speeds of movement. Maximum velocity of unloaded shortening (V0) and maximum force normalized to cross-sectional area (CSA) [specific tension (ST)] were measured in single 'skinned' skeletal muscle fibre segments.

    Results: Significant ageing- and gender-related differences were observed in muscle torque. A 33–55% ageing-related decline (P < 0.001) in maximum torque was observed irrespective of gender. At the single muscle fibre level, the ageing-related decline in knee-extensor muscle function was accompanied by a 20–28% decline in ST in muscle fibres expressing the type I MyHC isoform in both men and women, and a 29% decline in type IIa muscle fibre CSA, but the decreased fast-twitch fibre size was restricted to the men. Furthermore, in both men and women, V0 decreased in muscle cells expressing the type I and IIa MyHC isoforms.

    Conclusion: The present results provide evidence of specific ageing- and gender-related differences in regulation of muscle contraction at the cellular level. It is suggested that these cellular changes have a significant impact on muscle function and the ageing-related motor handicap.

    Keywords
    maximum velocity of unloaded shortening, muscle mass, skinned fibres, slack test, specific tension, torque-velocity
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:uu:diva-97417 (URN)10.1111/j.1748-1716.2007.01699.x (DOI)000247318600006 ()
    Available from: 2008-08-29 Created: 2008-08-29 Last updated: 2017-12-14Bibliographically approved
    2. Aging, muscle fiber type, and contractile function in sprint-trained athletes
    Open this publication in new window or tab >>Aging, muscle fiber type, and contractile function in sprint-trained athletes
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    2006 (English)In: Journal of applied physiology, ISSN 8750-7587, E-ISSN 1522-1601, Vol. 101, no 3, p. 906-917Article in journal (Refereed) Published
    Abstract [en]

    Biopsy samples were taken from the vastus lateralis of 18- to 84-yr-old male sprinters (n = 91). Fiber-type distribution, cross-sectional area, and myosin heavy chain (MHC) isoform content were identified using ATPase histochemistry and SDS-PAGE. Specific tension and maximum shortening velocity (V-o) were determined in 144 single skinned fibers from younger (18-33 yr, n = 8) and older (53-77 yr, n = 9) runners. Force-time characteristics of the knee extensors were determined by using isometric contraction. The cross-sectional area of type I fibers was unchanged with age, whereas that of type II fibers was reduced (P < 0.001). With age there was an increased MHC I (P < 0.01) and reduced MHC IIx isoform content (P < 0.05) but no differences in MHC IIa. Specific tension of type I and IIa MHC fibers did not differ between younger and older subjects. V-o of fibers expressing type I MHC was lower (P < 0.05) in older than in younger subjects, but there was no difference in V-o of type IIa MHC fibers. An aging-related decline of maximal isometric force (P < 0.001) and normalized rate of force development (P < 0.05) of knee extensors was observed. Normalized rate of force development was positively associated with MHC II (P < 0.05). The sprint-trained athletes experienced the typical aging-related reduction in the size of fast fibers, a shift toward a slower MHC isoform profile, and a lower V-o of type I MHC fibers, which played a role in the decline in explosive force production. However, the muscle characteristics were preserved at a high level in the oldest runners, underlining the favorable impact of sprint exercise on aging muscle.

    Keywords
    exercise, myosin heavy chain, single-fiber contractile properties, muscle strength
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:uu:diva-97418 (URN)10.1152/japplphysiol.00299.2006 (DOI)000240124100031 ()16690791 (PubMedID)
    Available from: 2008-08-29 Created: 2008-08-29 Last updated: 2017-12-14Bibliographically approved
    3. Effects of combined strength and sprint training on regulation of muscle contraction at the whole-muscle and single fibre levels in elite master sprinters
    Open this publication in new window or tab >>Effects of combined strength and sprint training on regulation of muscle contraction at the whole-muscle and single fibre levels in elite master sprinters
    Show others...
    2008 (English)In: Acta Physiologica, ISSN 1748-1708, E-ISSN 1748-1716, Vol. 193, no 3, p. 275-289Article in journal (Refereed) Published
    Abstract [en]

    AIM: This study aims at examining the effects of progressive strength and sprint training on regulation of muscle contraction at the whole-muscle and single-fibre levels in older sprint-trained athletes. METHODS: Eleven men (52-78 years) were randomized to a training (EX, n = 7) or control (CTRL, n = 4) group. EX participated in a 20-week programme that combined sprint training with heavy and explosive strength exercises, while CTRL maintained their usual run-based training schedules. RESULTS: EX improved maximal isometric and dynamic leg strength, explosive jump performance and force production in running. Specific tension and maximum shortening velocity of single fibres from the vastus lateralis were not altered in EX or CTRL. Fibre type and myosin heavy chain isoform distributions remained unchanged in the two groups. There was a general increase in fibre areas in EX, but this was significant only in IIa fibres. The 10% increase in squat jump in EX was accompanied by a 9% increase in the integrated EMG (iEMG) of the leg extensors but the 21-40% increases in isometric and dynamic strength were not paralleled by changes in iEMG. CONCLUSION: Adding strength training stimulus to the training programme improved maximal, explosive and sport-specific force production in elite master sprinters. These improvements were primarily related to hypertrophic muscular adaptations.

    Keywords
    ageing, fibre types, hypertrophy, master athletes, neural activity, skinned fibres
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:uu:diva-97419 (URN)10.1111/j.1748-1716.2008.01843.x (DOI)000256442100010 ()18284658 (PubMedID)
    Available from: 2008-08-29 Created: 2008-08-29 Last updated: 2017-12-14Bibliographically approved
    4. Effects of ageing and gender on the spatial organisation of nuclei in single human skeletal muscle cells
    Open this publication in new window or tab >>Effects of ageing and gender on the spatial organisation of nuclei in single human skeletal muscle cells
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    Manuscript (Other academic)
    Identifiers
    urn:nbn:se:uu:diva-97420 (URN)
    Available from: 2008-08-29 Created: 2008-08-29 Last updated: 2010-01-13Bibliographically approved
  • 19.
    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.

  • 20.
    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.

  • 21. 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.

  • 22. 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.

  • 23. 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.

  • 24.
    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.

  • 25. 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.

  • 26.
    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.

  • 27.
    Elfving, Karin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology and Infectious Medicine, Clinical Bacteriology. Center of Clinical Research, Dalarna, Falun, Sweden..
    Malmsten, Jonas
    Swedish Univ Agr Sci, Dept Clin Sci, Div Reprod, Uppsala, Sweden.;Natl Vet Inst, Dept Pathol & Wildlife Dis, S-75007 Uppsala, Sweden..
    Dalin, Anne-Marie
    Natl Vet Inst, Dept Pathol & Wildlife Dis, S-75007 Uppsala, Sweden..
    Nilsson, Kenneth
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology and Infectious Medicine, Clinical Bacteriology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases. Dalarna, Clin Res Ctr, Falun, Sweden..
    Serologic and Molecular Prevalence of Rickettsia helvetica and Anaplasma phagocytophilum in Wild Cervids and Domestic Mammals in the Central Parts of Sweden2015In: Vector Borne and Zoonotic Diseases, ISSN 1530-3667, E-ISSN 1557-7759, Vol. 15, no 9, p. 529-534Article in journal (Refereed)
    Abstract [en]

    Both Rickettsia helvetica and Anaplasma phagocytophilum are common in Ixodes ricinus ticks in Sweden. Knowledge is limited regarding different animal species' competence to act as reservoirs for these organism. For this reason, blood samples were collected from wild cervids (roe deer, moose) and domestic mammals (horse, cat, dog) in central Sweden, and sera were tested using immunofluorescence assay to detect antibodies against spotted fever rickettsiae using Rickettsia helvetica as antigen. Sera with a titer >= 1:64 were considered as positive, and 23.1% (104/450) of the animals scored positive. The prevalence of seropositivity was 21.5% (23/107) in roe deer, 23.3% (21/90) in moose, 36.5% (23/63) in horses, 22.1% (19/90) in cats, and 17.0% (17/100) in dogs. PCR analysis of 113 spleen samples from moose and sheep from the corresponding areas were all negative for rickettsial DNA. In roe deer, 85% (91/107) also tested seropositive for A. phagocytophilum with a titer cutoff of 1:128. The findings indicate that the surveyed animal species are commonly exposed to rickettsiae and roe deer also to A. phagocytophilum.

  • 28.
    Elmahalawy, Safaa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Single Nucleotide Polymorphism (SNP) in dyf7- 141 of Haemonchus contortus as potential marker for ivermectin resistance2017Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
    The full text will be freely available from 2018-12-26 11:28
  • 29. Eriksson, S.
    et al.
    Grandinson, K.
    Fikse, W. F.
    Lindberg, L.
    Mikko, S.
    Broström, H.
    Frey, R.
    Sundquist, M.
    Lindgren, Gabriella
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Genetic analysis of insect bite hypersensitivity (summer eczema) in Icelandic horses2008In: Animal, ISSN 1751-7311, Vol. 2, no 3, p. 360-365Article in journal (Refereed)
    Abstract [en]

    There is a lack of knowledge about the genetic background of eczema due to insect bite hypersensitivity, also called summer eczema, in horses. The condition is known in several horse breeds and countries and it causes reduced welfare of the horse and economic losses to the owner The aim of this study was to estimate genetic parameters for summer eczema in Swedish-born Icelandic horses. A questionnaire was sent to owners of horses sired by stallions with more than 50 offspring born in Sweden between 1991 and 2001. Variance components of summer eczema classified as healthy, mild, moderate or severe were estimated using the threshold methodology with sire models. In addition, summer eczema was analysed as a binary trait (healthy v. affected). The analyses included 1250 horses sired by 33 stallions. The prevalence of summer eczema was 8%, with a range of 0% to 30% in different paternal half-sib groups. Offspring of dams suffering from eczema had a higher risk of developing eczema. The heritability for severity of summer eczema was estimated at 0.3 (s.d. < 0.2) with a threshold sire model. In contrast to the age of the horse, different geographic areas and gender were significantly associated with severity of the eczema. We conclude that genetic selection could decrease the prevalence of summer eczema among Swedish-born Icelandic horses. The amount and quality of data are, however crucial for the possibility to introduce a genetic evaluation of summer eczema. The symptoms should be classified in several classes according to severity, and this classification could be made by the horse owner.

  • 30.
    Essner, Ann
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience. Evidensia Djursjukvård.
    On assessment methods related to pain in dogs with osteoarthritis2018Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    There is a need of valid and reliable assessment methods that are clinically applicable in canine rehabilitation practice. The aim of this thesis was to psychometrically evaluate measurement properties in assessment methods related to pain in naturally occurring canine osteoarthritis. Assessment methods developed for heart rate variability analysis, i.e. Polar heart rate monitor, and owner-reported perceptions of pain severity and pain interference with functionality, i.e. Canine Brief Pain Inventory, were tested.

    Methods: Four observational studies were conducted. Study I was a cross-sectional study consisting of two groups of consecutively recruited dogs. The Canine Brief Pain Inventory was administered to owners of dogs with naturally occurring osteoarthritis (n=61) and clinically sound dogs (n=21). Study II was a descriptive and correlative cross-sectional study based on the same sample of dogs with osteoarthritis (n=71), assessing chronic pain behavior and associations between explanatory variables and chronic pain behavior. Study III and IV were correlative studies, assessing Polar heart rate monitor measuring interbeat intervals and time- and frequency-based heart rate variability parameters, compared to simultaneously recorded electrocardiogram in dogs (n=11).

    Results: High internal consistencies and ability to discriminate sound dogs from osteoarthritis dogs were found. The hypothesis of the presented two-factor structure of the Canine Brief Pain Inventory was rejected. Owners reported higher proportions of chronic pain behavior in items targeting physical activities, e.g. getting up, moving after rest and moving after major exercise. A minor proportion of dogs with osteoarthritis showed no owner-perceived behavioural signs of chronic pain. Owner observations were not associated with ongoing antiinflammatory medications. In Study III and IV, 595 errors (12.3%) were identified in Polar data. The number of errors were unequally distributed among the dogs. Interbeat intervals and heart rate variability parameters from electrocardiogram and Polar were strongly associated. Standard error of measurements were high among some heart rate variability parameters in Polar and electrocardiogram.

    In conclusion, this thesis contributes to our knowledge about assessment methods related to diverse components of pain in dogs with osteoarthritis, allowing improved pain management in clinical practice.

    List of papers
    1. Psychometric evaluation of the canine brief pain inventory in a Swedish sample of dogs with pain related to osteoarthritis
    Open this publication in new window or tab >>Psychometric evaluation of the canine brief pain inventory in a Swedish sample of dogs with pain related to osteoarthritis
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    2017 (English)In: Acta Veterinaria Scandinavica, ISSN 1751-0147, E-ISSN 1751-0147, Vol. 59, article id 44Article in journal (Refereed) Published
    Abstract [en]

    Background: To evaluate intervention, implement evidence-based practice and enhance the welfare of dogs with naturally occurring osteoarthritis (OA), access to valid, reliable and clinically relevant outcome measures is crucial for researchers, veterinarians and rehabilitation practitioners. The objectives of the present study were to translate and evaluate psychometric properties, in terms of internal consistency and construct validity, of the owner-reported measure canine brief pain inventory (CBPI) in a Swedish sample of dogs with pain related to OA. Results: Twenty-one owners of clinically sound dogs and 58 owners of dogs with pain related to OA were included in this observational and cross-sectional study. After being translated according to the guidelines for patient-reported outcome measures, the CBPI was completed by the canine owners. Construct validity was assessed by confirmatory factor analysis, by repeating the principal component analysis and by assessing for differences between clinically sound dogs and dogs with pain related to OA. Internal consistency was estimated by Cronbach's a. Confirmatory factor analysis was not able to confirm the factor-structure models tested in our sample. Principal component analysis showed a two-component structure, pain severity and pain interference of function. Two components accounted for 76.8% of the total variance, suggesting an acceptable fit of a two-component structure. The ratings from the clinically sound dogs differed from OA dogs and showed significantly lower CBPI total sum. Cronbach's a was 0.94 for the total CBPI, 0.91 for the pain severity and 0.91 for the pain interference of function. Conclusions: The results indicate that the translated version of the CBPI is valid for use in the Swedish language. The findings suggest satisfying psychometric properties in terms of high internal consistencies and ability to discriminate clinically sound dogs from OA dogs. However, based on the confirmatory factor analysis, the original factor structure in the CBPI is not ideally suited to measure pain related to OA in our sample and the hypothesis of the presented two-factor structure was rejected. Further research needs to be conducted to determine whether the original psychometric results from CBPI can be replicated across different target groups and particularly with larger sample size.

    Keywords
    CBPI, Dogs, Measurement properties, Osteoarthritis, Pain, Physiotherapy, Rehabilitation
    National Category
    Veterinary Science
    Identifiers
    urn:nbn:se:uu:diva-330036 (URN)10.1186/s13028-017-0311-2 (DOI)000404805500001 ()
    Available from: 2017-09-29 Created: 2017-09-29 Last updated: 2017-12-05
    2. Owner-perceived chronic pain behavior and associated factors in canine osteoarthritis – an observational study
    Open this publication in new window or tab >>Owner-perceived chronic pain behavior and associated factors in canine osteoarthritis – an observational study
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    (English)In: Article in journal (Refereed) Submitted
    National Category
    Physiotherapy Veterinary Science
    Research subject
    Physiotherapy
    Identifiers
    urn:nbn:se:uu:diva-335286 (URN)
    Available from: 2017-12-03 Created: 2017-12-03 Last updated: 2017-12-05
    3. Comparison of Polar RS800CX heart rate monitor and electrocardiogram for measuring inter-beat intervals in healthy dogs
    Open this publication in new window or tab >>Comparison of Polar RS800CX heart rate monitor and electrocardiogram for measuring inter-beat intervals in healthy dogs
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    2015 (English)In: Physiology and Behavior, ISSN 0031-9384, E-ISSN 1873-507X, Vol. 138, p. 247-253Article in journal (Refereed) Published
    Abstract [en]

    The aim of the present study was to assess the criterion validity, relative reliability and level of agreement of Polar RS800CX heart rate monitor measuring inter-beat intervals (IBIs), compared to simultaneously recorded electrocardiogram (ECG) in dogs. METHODS: Five continuous minutes of simultaneously recorded IBIs from Polar RS800CX and Cardiostore ECG in 11 adult healthy dogs maintaining standing position were analyzed. Polar data was statistically compared to ECG data to assess for systematic differences between the methods. Three different methods for handling missing IBI data were used. Criterion validities were calculated by intraclass correlation coefficients (ICCs) and corresponding 95% confidence intervals (CIs). Relative reliabilities and levels of agreement were calculated by ICCs and the Bland and Altman analysis for repeated measurements per subject. RESULTS: Correlation coefficients between IBI data from ECG and Polar RS800CX varied between 0.73 and 0.84 depending on how missing values were handled. Polar was over- and underestimating IBI data compared to ECG. The mean difference in log transformed (base10) IBI data was 0.8%, and 93.2% of the values were within the limits of agreement. Internally excluding three subjects presenting IBI series containing more than 5% erroneous IBIs resulted in ICCs between 0.97 and 0.99. Bland and Altman analysis (n=8) showed mean difference was 1.8ms, and 98.5% of the IBI values were plotted inside limits of agreement. CONCLUSION: This study showed that Polar systematically biased recorded IBI series and that it was fundamental to detect measurement errors. For Polar RS800CX heart rate monitor to be used interchangeably to ECG, by showing excellent criterion validity and reliable IBI measures in group and individual samples, only less than 5% of artifacts could be accepted.

    National Category
    Neurosciences
    Identifiers
    urn:nbn:se:uu:diva-239083 (URN)10.1016/j.physbeh.2014.10.034 (DOI)000348882900034 ()25446208 (PubMedID)
    Available from: 2015-01-06 Created: 2014-12-18 Last updated: 2018-01-11Bibliographically approved
    4. Validity and reliability properties of canine short-term heart rate variability measures - a pilot study
    Open this publication in new window or tab >>Validity and reliability properties of canine short-term heart rate variability measures - a pilot study
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    2015 (English)In: Journal of Veterinary Behavior: Clinical Applications and Research, ISSN 1558-7878, E-ISSN 1878-7517, Vol. 10, no 5, p. 384-390Article in journal (Refereed) Published
    Abstract [en]

    The objective of the pilot study was to compare validity and reliability properties of Polar RS800CX (Polar Electro Oy, Kempele, Finland) against simultaneously recorded electrocardiogram (ECG) measuring time-and frequency-based short-term heart rate variability (HRV) parameters, in dogs during stationary standing position. Five-minute recordings with less than 5% error rates from inter-beat interval (IBI) series obtained by Polar RS800CX and ECG, in 8 adult dogs, were used for HRV analysis. Polar data were statistically compared to the ECG data to assess for systematic differences in time-and frequency-based HRV parameters. Relative and absolute reliabilities were estimated by intraclass correlation coefficient, Spearman rho, Bland and Altman analysis, standard error of measurement, and standard error of measurements in percentage. Paired t test was used to determine the statistical significance of differences between the measurement methods. Results: There were high correlation coefficients between HRV parameters obtained from Polar RS800CX and ECG. Intraclass correlation coefficients were 0.98-1.00, and Spearman r was 0.93-0.98. There were differences between the methods in 2 HRV parameters, the standard deviation of normal-to-normal IBIs (SDNN) (P = 0.035) and the square root of the mean squared differences of successive normal-to normal IBIs (RMSSD) (P = 0.034). Standard error of measurements was between 2.8-11.6% in ECG and between 2.6-11.8% in Polar, indicating rather high measurement error in 3 of the HRV parameters in both measurement methods. Close agreements and high correlation estimates in this pilot study indicated acceptable relative reliability in Polar RS800CX measuring time-and frequency-based HRV parameters in the group of dogs studied. However, the present pilot study revealed differences between Polar RS800CX and ECG in time-based standard deviation of normal-to-normal and square root of the mean squared differences of successive normal-to normal parameters, and that small amounts of erroneous IBI segments from Polar negatively impact on the validity and reliability properties of Polar RS800CX.

    Keywords
    behavior, dogs, heart rate variability, reliability, validity
    National Category
    Veterinary Science
    Identifiers
    urn:nbn:se:uu:diva-264313 (URN)10.1016/j.jveb.2015.05.006 (DOI)000360648200003 ()
    Available from: 2015-10-15 Created: 2015-10-09 Last updated: 2018-01-09Bibliographically approved
  • 31.
    Essner, Ann
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Zetterberg, Lena (Contributor)
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Hellström, Karin (Contributor)
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Sjöström, Rita (Contributor)
    Umeå Universitet, Institutionen för samhällsmedicin och rehabilitering.
    Gustås, Pia (Contributor)
    Sveriges lantbruksuniversitet, Institutionen för kliniska vetenskaper.
    Owner-perceived chronic pain behavior and associated factors in canine osteoarthritis – an observational studyIn: Article in journal (Refereed)
  • 32.
    Essner, Ann
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Physiotherapy.
    Sjostrom, Rita
    Reg Jamtland Harjedalen, Unit Res Educ & Dev, Ostersund, Sweden.;Mid Sweden Univ, Dept Hlth Sci, Ostersund, Sweden..
    Gustas, Pia
    Swedish Univ Agr Sci, Dept Clin Sci, Uppsala, Sweden..
    Edge-Hughes, Laurie
    Canine Fitness Ctr, Calgary, AB, Canada..
    Zetterberg, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Physiotherapy.
    Hellström, Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Physiotherapy. Uppsala Univ, Dept Neurosci, Sect Physiotherapy, Uppsala, Sweden..
    Validity and reliability properties of canine short-term heart rate variability measures - a pilot study2015In: Journal of Veterinary Behavior: Clinical Applications and Research, ISSN 1558-7878, E-ISSN 1878-7517, Vol. 10, no 5, p. 384-390Article in journal (Refereed)
    Abstract [en]

    The objective of the pilot study was to compare validity and reliability properties of Polar RS800CX (Polar Electro Oy, Kempele, Finland) against simultaneously recorded electrocardiogram (ECG) measuring time-and frequency-based short-term heart rate variability (HRV) parameters, in dogs during stationary standing position. Five-minute recordings with less than 5% error rates from inter-beat interval (IBI) series obtained by Polar RS800CX and ECG, in 8 adult dogs, were used for HRV analysis. Polar data were statistically compared to the ECG data to assess for systematic differences in time-and frequency-based HRV parameters. Relative and absolute reliabilities were estimated by intraclass correlation coefficient, Spearman rho, Bland and Altman analysis, standard error of measurement, and standard error of measurements in percentage. Paired t test was used to determine the statistical significance of differences between the measurement methods. Results: There were high correlation coefficients between HRV parameters obtained from Polar RS800CX and ECG. Intraclass correlation coefficients were 0.98-1.00, and Spearman r was 0.93-0.98. There were differences between the methods in 2 HRV parameters, the standard deviation of normal-to-normal IBIs (SDNN) (P = 0.035) and the square root of the mean squared differences of successive normal-to normal IBIs (RMSSD) (P = 0.034). Standard error of measurements was between 2.8-11.6% in ECG and between 2.6-11.8% in Polar, indicating rather high measurement error in 3 of the HRV parameters in both measurement methods. Close agreements and high correlation estimates in this pilot study indicated acceptable relative reliability in Polar RS800CX measuring time-and frequency-based HRV parameters in the group of dogs studied. However, the present pilot study revealed differences between Polar RS800CX and ECG in time-based standard deviation of normal-to-normal and square root of the mean squared differences of successive normal-to normal parameters, and that small amounts of erroneous IBI segments from Polar negatively impact on the validity and reliability properties of Polar RS800CX.

  • 33.
    Essner, Ann
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience. Evidensia Djursjukvård.
    Sjöström, Rita
    Umeå Universitet, Institutionen för samhällsmedicin och rehabilitering.
    Zetterberg, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Hellström, Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Gustås, Pia
    Sveriges lantbruksuniversitet, Institutionen för kliniska vetenskaper.
    Högberg, Hans
    Högskolan i Gävle, Avdelningen för medicin- och vårdvetenskap.
    Test–retest reliability in a translated version of the Canine Brief Pain Inventory in canine osteoarthritis2016In: Proceedings of the 9th international symposium on veterinary rehabilitation and physical therapy: Test–retest reliability in a translated version of the Canine Brief Pain Inventory in canine osteoarthritis / [ed] Acta Veterinaria Scandinavica, 2016, Vol. 58, p. A10:85-, article id Suppl 2Conference paper (Refereed)
  • 34.
    Essner, Ann
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Physiotherapy. Evidensia Djurkliniken Gefle, Gävle, Sweden.
    Zetterberg, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Physiotherapy.
    Hellström, Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Physiotherapy.
    Gustas, Pia
    Swedish Univ Agr Sci, Fac Vet Med & Anim Husb, Dept Clin Sci, Box 7054, S-75007 Uppsala, Sweden..
    Högberg, Hans
    Univ Gavle, Fac Hlth & Occupat Studies, Dept Hlth & Caring Sci, S-80176 Gavle, Sweden..
    Sjöström, Rita
    Reg Jamtland Harjedalen, Unit Res Educ & Dev, Box 654, S-83127 Ostersund, Sweden.;Umea Univ, Fac Physiotherapy, Dept Community Med & Rehabil, S-90187 Umea, Sweden..
    Psychometric evaluation of the canine brief pain inventory in a Swedish sample of dogs with pain related to osteoarthritis2017In: Acta Veterinaria Scandinavica, ISSN 1751-0147, E-ISSN 1751-0147, Vol. 59, article id 44Article in journal (Refereed)
    Abstract [en]

    Background: To evaluate intervention, implement evidence-based practice and enhance the welfare of dogs with naturally occurring osteoarthritis (OA), access to valid, reliable and clinically relevant outcome measures is crucial for researchers, veterinarians and rehabilitation practitioners. The objectives of the present study were to translate and evaluate psychometric properties, in terms of internal consistency and construct validity, of the owner-reported measure canine brief pain inventory (CBPI) in a Swedish sample of dogs with pain related to OA. Results: Twenty-one owners of clinically sound dogs and 58 owners of dogs with pain related to OA were included in this observational and cross-sectional study. After being translated according to the guidelines for patient-reported outcome measures, the CBPI was completed by the canine owners. Construct validity was assessed by confirmatory factor analysis, by repeating the principal component analysis and by assessing for differences between clinically sound dogs and dogs with pain related to OA. Internal consistency was estimated by Cronbach's a. Confirmatory factor analysis was not able to confirm the factor-structure models tested in our sample. Principal component analysis showed a two-component structure, pain severity and pain interference of function. Two components accounted for 76.8% of the total variance, suggesting an acceptable fit of a two-component structure. The ratings from the clinically sound dogs differed from OA dogs and showed significantly lower CBPI total sum. Cronbach's a was 0.94 for the total CBPI, 0.91 for the pain severity and 0.91 for the pain interference of function. Conclusions: The results indicate that the translated version of the CBPI is valid for use in the Swedish language. The findings suggest satisfying psychometric properties in terms of high internal consistencies and ability to discriminate clinically sound dogs from OA dogs. However, based on the confirmatory factor analysis, the original factor structure in the CBPI is not ideally suited to measure pain related to OA in our sample and the hypothesis of the presented two-factor structure was rejected. Further research needs to be conducted to determine whether the original psychometric results from CBPI can be replicated across different target groups and particularly with larger sample size.

  • 35. Etterlin, P. E.
    et al.
    Ekman, S.
    Strand, Robin
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Division of Visual Information and Interaction. Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Computerized Image Analysis and Human-Computer Interaction.
    Olstad, K.
    Ley, C. J.
    Osteochondrosis, Synovial Fossae, and Articular Indentations in the Talus and Distal Tibia of Growing Domestic Pigs and Wild Boars2017In: Veterinary pathology, ISSN 0300-9858, E-ISSN 1544-2217, Vol. 54, no 3, p. 445-456Article in journal (Refereed)
  • 36.
    Etterlin, Pernille Engelsen
    et al.
    Swedish Univ Agr Sci SLU, Dept Biomed Sci & Vet Publ Hlth, Sect Pathol, S-75007 Uppsala, Sweden..
    Morrison, David A.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Systematic Biology.
    Osterberg, Julia
    Natl Vet Inst SVA, S-75189 Uppsala, Sweden..
    Ytrehus, Bjornar
    Norwegian Inst Nat Res NINA, Terr Ecol Dept, N-7485 Trondheim, Norway..
    Heldmer, Eva
    Swedish Anim Hlth Serv SvDHV, S-46432 Mellerud, Sweden..
    Ekman, Stina
    Swedish Univ Agr Sci SLU, Dept Biomed Sci & Vet Publ Hlth, Sect Pathol, S-75007 Uppsala, Sweden..
    Osteochondrosis, but not lameness, is more frequent among free-range pigs than confined herd-mates2015In: ACTA VETERINARIA SCANDINAVICA, ISSN 0044-605X, Vol. 57, article id 63Article in journal (Refereed)
    Abstract [en]

    Background: Organic pig production is expanding and amongst the objectives of organic farming are enhancing animal health and welfare. However, some studies have reported a higher prevalence of lameness and joint condemnation at slaughter in free-range/organic pigs than in conventionally raised pigs. Organic slaughter pigs have free-range housing in which indoor and outdoor access is compulsory, while in conventional farming the pigs are commonly confined to indoor pens. The present study evaluated the effects of free-range and confined housing on lameness prevalence in a herd of 106 finisher pigs, and whether osteochondrosis and Erysipelothrix rhusiopathiae associated arthritis influences these effects. We also evaluated the association between clinical lameness during the rearing period and joint condemnations at slaughter. Results: Seventy free-range and 36 confined housed fattener pigs were scored for their gait twice during the rearing period and 848 joints were evaluated post mortem. Osteochondrosis was more frequent among free-range than confined pigs (P < 0.05), and when present it was also more severe (P < 0.001). Pigs with more numerous and more severe osteochondral lesions had their gait affected more than did pigs with fewer such lesions (P < 0.05). Hence it was a paradox that we did not detect more lameness among the free-range pigs than the confined pigs. E. rhusiopathiae associated arthritis was not diagnosed. The association between gait remarks/clinical lameness and joint condemnations at slaughter was not significant. Conclusions: The results indicate that free-range housing may have both positive and negative effects on locomotory traits. Free-range pigs may be less clinically affected by osteochondrosis than are confined pigs. One explanation for this effect may be strengthening of joint supportive tissue and pain relief promoted by exercise. Visual gait scoring missed serious joint lesions that probably were harmful to the pigs, and should therefore not be used as a sole indicator of joint/leg health in welfare inspection of pigs. The association between gait scores and joint condemnation appeared to be poor. This study was limited to one herd, and so more and larger studies on the effects of free-range housing on lameness severity and osteochondrosis development in pigs are recommended.

  • 37. Fall, T
    et al.
    Hedhammar, A
    Wallberg, A
    Fall, N
    Ahlgren, Kerstin M.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Hamlin, H. H.
    Lindblad-Toh, Kerstin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Andersson, G.
    Kämpe, Olle
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Diabetes Mellitus in Elkhounds Is Associated with Diestrus and Pregnancy2010In: Journal of Veterinary Internal Medicine, ISSN 0891-6640, E-ISSN 1939-1676, Vol. 24, no 6, p. 1322-1328Article in journal (Refereed)
    Abstract [en]

    Background: Female Elkhounds are shown to be at increased risk for diabetes mellitus, and occurrence of diabetes during pregnancy has been described in several cases. Hypothesis: Onset of diabetes mellitus in Elkhounds is associated with diestrus. Animals: Sixty-three Elkhounds with diabetes mellitus and 26 healthy controls. Methods: Medical records from 63 Elkhounds with diabetes were reviewed and owners were contacted for follow-up information. Blood samples from the day of diagnosis were available for 26 dogs. Glucose, fructosamine, C-peptide, growth hormone (GH), insulin-like growth factor-1, progesterone, and glutamate decarboxylase isoform 65-autoantibodies were analyzed and compared with 26 healthy dogs. Logistic models were used to evaluate the association of clinical variables with the probability of diabetes and with permanent diabetes mellitus after ovariohysterectomy (OHE). Results: All dogs in the study were intact females and 7 dogs (11%) were pregnant at diagnosis. The 1st clinical signs of diabetes mellitus occurred at a median of 30 days (interquartile range [IQR], 3-45) after estrus, and diagnosis was made at a median of 46 days (IQR, 27-62) after estrus. Diabetes was associated with higher concentrations of GH and lower concentrations of progesterone compared with controls matched for time after estrus. Forty-six percent of dogs that underwent OHE recovered from diabetes with a lower probability of remission in dogs with higher glucose concentrations (odds ratio [OR], 1.2; P = .03) at diagnosis and longer time (weeks) from diagnosis to surgery (OR, 1.5; P = .05). Conclusions: Diabetes mellitus in Elkhounds develops mainly during diestrus and pregnancy. Immediate OHE improves the prognosis for remission of diabetes.

  • 38. Fall, T.
    et al.
    Holm, B.
    Karlsson, Å.
    Ahlgren, Kerstin M.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Kämpe, Olle
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    von Euler, H.
    Glucagon stimulation test for estimating endogenous insulin secretion in dogs2008In: The Veterinary Record, ISSN 0042-4900, E-ISSN 2042-7670, Vol. 163, no 9, p. 266-270Article in journal (Refereed)
    Abstract [en]

    Fifty-one dogs (27 diabetic dogs, four that had recovered from diabetes and 20 healthy control dogs) were given 0.5 or 1.0 mg glucagon intravenously. Blood samples were taken before the injection and 10 and 20 minutes after it. Samples were analysed to determine C-peptide, insulin and glucose concentrations, and one sample from each dog was analysed for fructosamine. The median (interquartile range) concentrations of C-peptide in the samples taken at 10 minutes were 0.5 (0.3 to 0.8) nmol/l in the control dogs, 0.1 (0 to 0.2) nmol/l in the diabetic dogs, and 0.3 (0.2 to 0.4) nmol/l in the dogs that had recovered from diabetes. Seven of the 51 dogs showed mild adverse reactions after the injection of glucagon.

  • 39. Fall, Tove
    et al.
    Hamlin, Helene Hansson
    Hedhammar, Åke
    Kämpe, Olle
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Egenvall, Agneta
    Diabetes mellitus in a population of 180,000 insured dogs: incidence, survival, and breed distribution2007In: Journal of Veterinary Internal Medicine, ISSN 0891-6640, E-ISSN 1939-1676, Vol. 21, no 6, p. 1209-1216Article in journal (Refereed)
    Abstract [en]

    Background: Canine diabetes mellitus (DM) is a common endocrinopathy with an unclear etiology. For a better understanding of the underlying mechanisms, there is a need for comprehensive epidermiologic studies. Earlier studies have shown that the risk of disease is higher in certain dog breeds. Hypothesis: Incidence, age of onset, survival and sex proportion of DM vary by breed. Animals: Data from a cohort of 182,087 insured dogs aged 5-12 years accounting for 652,898 dog-years at risk were studied retrospectively. Methods: Incidence rates by sex, breed, and geography were calculated with exact denominators. Age-specific incidence and survival after 1st DM claim were computed with Cox's regression and Kaplan-Meier survival function. Multivariable survival analysis was performed for the outcome diagnosis of DM with age, sex, and geography tested as fixed effects, previous endocrine or pancreatic diseases tested as time-dependent covariates, and breed tested as a random effect. Results: The mean age at 1st insurance claim for the 860 DM dogs (72% females) was 8.6 years. The incidence of DM was 13 cases per 10,000 dog-years at risk. Australian Terriers, Samoyeds, Swedish Elkhounds, and Swedish Lapphunds were found to have the highest incidence. The proportion of females with DM varied significantly among breeds. Swedish Elkhounds, Beagles, Norwegian Elkhounds, and Border Collies that developed DM were almost exclusively females. The multivariable model showed that breed, previous hyperadrenocorticism, and female sex were risk factors for developing DM. Median survival time was 57 days after 1st claim. Excluding the 223 dogs that died within I day, the median survival time was 2 years after 1st claim of DM. Conclusion: The significant breed-specific sex and age differences shown in this study indicate that genetic variation could make breeds more or less susceptible to different types of DM.

  • 40.
    Fegraeus, Kim Jäderkvist
    et al.
    Swedish Univ Agr Sci, Dept Anim Breeding & Genet, Uppsala, Sweden..
    Lawrence, Chameli
    Swedish Univ Agr Sci, Dept Anim Breeding & Genet, Uppsala, Sweden..
    Petäjistö, Katrine
    Swedish Univ Agr Sci, Dept Anim Breeding & Genet, Uppsala, Sweden..
    Johansson, Maria K.
    Swedish Univ Agr Sci, Dept Anim Breeding & Genet, Uppsala, Sweden..
    Wiklund, Maja
    Swedish Univ Agr Sci, Dept Clin Sci, Uppsala, Sweden..
    Olsson, Christina
    Swedish Trotting Assoc, Bromma, Sweden..
    Andersson, Leif
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Swedish Univ Agr Sci, Dept Anim Breeding & Genet, Uppsala, Sweden.;Texas A&M Univ, Dept Vet Integrat Biosci, College Stn, TX USA..
    Andersson, Lisa S.
    Capilet Genet AB, Vasteras, Sweden..
    Roed, Knut H.
    Norwegian Univ Life Sci, Dept Basic Sci & Aquat Med, Fac Vet Med, Oslo, Norway..
    Ihler, Carl-Fredrik
    Norwegian Univ Life Sci, Dept Compan Anim Clin Sci, Fac Vet Med, Oslo, Norway..
    Strand, Eric
    Norwegian Univ Life Sci, Dept Compan Anim Clin Sci, Fac Vet Med, Oslo, Norway..
    Lindgren, Gabriella
    Swedish Univ Agr Sci, Dept Anim Breeding & Genet, Uppsala, Sweden..
    Velie, Brandon D.
    Swedish Univ Agr Sci, Dept Anim Breeding & Genet, Uppsala, Sweden..
    Lack of significant associations with early career performance suggest no link between the DMRT3 "Gait Keeper" mutation and precocity in Coldblooded trotters2017In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 12, no 5, article id e0177351Article in journal (Refereed)
    Abstract [en]

    The Swedish-Norwegian Coldblooded trotter (CBT) is a local breed in Sweden and Norway mainly used for harness racing. Previous studies have shown that a mutation from cytosine (C) to adenine (A) in the doublesex and mab-3 related transcription factor 3 (DMRT3) gene has a major impact on harness racing performance of different breeds. An association of the DMRT3 mutation with early career performance has also been suggested. The aim of the current study was to investigate this proposed association in a randomly selected group of CBTs. 769 CBTs (485 raced, 284 unraced) were genotyped for the DMRT3 mutation. The association with racing performance was investigated for 13 performance traits and three different age intervals: 3 years, 3 to 6 years, and 7 to 10 years of age, using the statistical software R. Each performance trait was analyzed for association with DMRT3 using linear models. The results suggest no association of the DMRT3 mutation with precocity (i.e. performance at 3 years of age). Only two traits (race time and number of disqualifications) were significantly different between the genotypes, with AA horses having the fastest times and CC horses having the highest number of disqualifications at 3 years of age. The frequency of the AA genotype was significantly lower in the raced CBT sample compared with the unraced sample and less than 50% of the AA horses participated in a race. For the age intervals 3 to 6 and 7 to 10 years the AA horses also failed to demonstrate significantly better performance than the other genotypes. Although suggested as the most favorable genotype for racing performance in Standardbreds and Finnhorses across all ages, the AA genotype does not appear to be associated with superior performance, early or late, in the racing career of CBTs.

  • 41.
    Fuchs, Dieter
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Cell Biology.
    Novel Treatment Modalities for High-Risk Neuroblastoma: Studies in Animal Models2009Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Neuroblastoma, the most common extracranial solid tumor of childhood, is a heterogeneous tumor. In some patients, the tumor can go into spontaneous regression and disappear whereas other patients have rapidly growing tumors with a poor prognosis. The overall long-term survival rate in patients with high-risk neuroblastoma is less than 30%, indicating the need for new treatment strategies.

    Angiogenesis inhibition hampers the formation of new blood vessels, thereby limiting the tumors’ metabolic exchange. Neuroblastoma is rapidly growing and high tumor angiogenesis has been associated with poor outcome. Therefore, the aim of this thesis was to investigate the effect of novel treatment modalities for angiogenesis inhibition on high-risk neuroblastoma xenografts. For that purpose, we used subcutaneous mouse models and characterized orthotopic mouse models for high-risk neuroblastoma.

    We found that xenotransplantation of neuroblastoma cells into the adrenal gland of SCID and SCID beige mice resulted in orthotopic tumors resembling clinical neuroblastoma in respect to tumor site, growth and spread. Using contrast-enhanced ultrasound, we observed that the receptor tyrosine kinase inhibitor SU11248 reduced orthotopic neuroblastoma growth and spread by reducing tumor angiogenesis.

    In subcutaneous xenografts for high-risk neuroblastoma, valuable for studies requiring continuous assessment of tumor volume, we demonstrated that immune-neutralizing VEGF with the anti-VEGF antibody bevacizumab significantly reduced neuroblastoma growth.

    Finally, we found that formulations of the chemotherapeutic drug GMX1778 inhibited angiogenesis and induced tumor regression in a dose dependent manner without host toxicity. We showed that relapsing tumors remained responsive to GMX-therapy without accelerated growth or induced drug resistance.

    In conclusion, SU11248, bevacizumab, and formulations of the active compound GMX1778 may become useful for treating high-risk neuroblastoma.

    List of papers
    1. The Anti-VEGF Antibody Bevacizumab Potently Reduces the Growth Rate of High-Risk Neuroblastoma Xenografts
    Open this publication in new window or tab >>The Anti-VEGF Antibody Bevacizumab Potently Reduces the Growth Rate of High-Risk Neuroblastoma Xenografts
    Show others...
    2006 (English)In: Pediatric Research, ISSN 0031-3998, E-ISSN 1530-0447, Vol. 60, no 5, p. 576-581Article in journal (Refereed) Published
    Abstract [en]

    Neuroblastoma (NB) is a rapidly growing, well-vascularized childhood cancer that often presents with metastases. The overall five-year survival in NB is approximately 45% despite multimodality treatment, and therefore there is a clinical need for new therapeutic strategies. NB frequently overexpresses the angiogenic factor VEGF (vascular endothelial growth factor). The aim of this study was to investigate the effect of bevacizumab (Avastin, Genentech/Roche), a humanized anti-VEGF-A antibody, on NB growth in three different xenograft models, chosen to resemble high-risk NB. The human NB cell lines SK-N-AS, IMR-32 and SH-SY5Y, which are poorly differentiated and overexpress VEGF-A, were injected s.c. in immunodeficient mice. Bevacizumab was given intraperitoneally twice weekly at 5 mg/kg body weight, starting at a tumor volume of 0.3 mL. Bevacizumab significantly (p < 0.01-0.05) reduced NB growth in vivo without toxicity by causing a 30-63% reduction of angiogenesis, but had no effect on NB cell survival in vitro. Serum concentrations of VEGF-A increased two- to six-fold during bevacizumab therapy which did not result in faster tumor growth compared with control animals. Based on our experimental data we suggest consideration of bevacizumab in treatment of high-risk NB that does not respond to conventional therapy and that overexpresses VEGF.

    Keywords
    angiogenesis, bevacizumab, neuroblastoma, VEGF-A, human
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:uu:diva-98023 (URN)10.1203/01.pdr.0000242494.94000.52 (DOI)000241570300013 ()16988184 (PubMedID)
    Available from: 2009-02-06 Created: 2009-02-06 Last updated: 2017-12-14Bibliographically approved
    2. Regression of orthotopic neuroblastoma in mice by targeting the endothelial and tumor cell compartments
    Open this publication in new window or tab >>Regression of orthotopic neuroblastoma in mice by targeting the endothelial and tumor cell compartments
    Show others...
    2009 (English)In: Journal of Translational Medicine, ISSN 1479-5876, E-ISSN 1479-5876, Vol. 7, p. 16-Article in journal (Refereed) Published
    Abstract [en]

    BACKGROUND: High-risk neuroblastoma has an overall five-year survival of less than 40%, indicating a need for new treatment strategies such as angiogenesis inhibition. Recent studies have shown that chemotherapeutic drugs can inhibit angiogenesis if administered in a continuous schedule. The aim of this study was primarily to characterize tumor spread in an orthotopic, metastatic model for aggressive, MYCN-amplified neuroblastoma and secondarily to study the effects of daily administration of the chemotherapeutic agent CHS 828 on tumor angiogenesis, tumor growth, and spread. METHODS: MYCN-amplified human neuroblastoma cells (IMR-32, 2 x 10(6)) were injected into the left adrenal gland in SCID mice through a flank incision. Nine weeks later, a new laparotomy was performed to confirm tumor establishment and to estimate tumor volume. Animals were randomized to either treatment with CHS 828 (20 mg/kg/day; p.o.) or vehicle control. Differences between groups in tumor volume were analyzed by Mann-Whitney U test and in metastatic spread using Fisher's exact test. Differences with p < 0.05 were considered statistically significant. RESULTS: The orthotopic model resembled clinical neuroblastoma in respect to tumor site, growth and spread. Treatment with CHS 828 resulted in tumor regression (p < 0.001) and reduction in viable tumor fraction (p < 0.001) and metastatic spread (p < 0.05) in correlation with reduced plasma levels of the putative tumor marker chromogranin A (p < 0.001). These effects were due to increased tumor cell death and reduced angiogenesis. No treatment-related toxicities were observed. CONCLUSION: The metastatic animal model in this study resembled clinical neuroblastoma and is therefore clinically relevant for examining new treatment strategies for this malignancy. Our results indicate that daily scheduling of CHS 828 may be beneficial in treating patients with high-risk neuroblastoma.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:uu:diva-98024 (URN)10.1186/1479-5876-7-16 (DOI)000265143500001 ()19284605 (PubMedID)
    Available from: 2009-02-06 Created: 2009-02-06 Last updated: 2017-12-14Bibliographically approved
    3. SU11248-mediated angiogenesis inhibition reduces tumor growth and spread in orthotopic neuroblastoma in mice monitored with contrast-enhanced ultrasound
    Open this publication in new window or tab >>SU11248-mediated angiogenesis inhibition reduces tumor growth and spread in orthotopic neuroblastoma in mice monitored with contrast-enhanced ultrasound
    (English)Article in journal (Refereed) Submitted
    Identifiers
    urn:nbn:se:uu:diva-98025 (URN)
    Available from: 2009-02-06 Created: 2009-02-06 Last updated: 2011-01-11Bibliographically approved
    4. Metronomic GMX1777 results in tumor regression and vessel maturation in subcutaneous neuroblastoma in mice without inducing drug resistance
    Open this publication in new window or tab >>Metronomic GMX1777 results in tumor regression and vessel maturation in subcutaneous neuroblastoma in mice without inducing drug resistance
    Show others...
    (English)Manuscript (Other academic)
    Identifiers
    urn:nbn:se:uu:diva-98026 (URN)
    Available from: 2009-02-06 Created: 2009-02-06 Last updated: 2011-06-28Bibliographically approved
  • 42.
    Gallwitz, Maike
    et al.
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Cell and Molecular Biology. Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Cell and Molecular Biology, Molecular Immunology. Molekylär immunologi.
    Hellman, Lars
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Cell and Molecular Biology. Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Cell and Molecular Biology, Molecular Immunology. Molekylär immunologi.
    Rapid species-specific diversification of the mast cell chymase locus during mammalian evolution.2006In: Immunogenetics, Vol. 58, p. 641-654Article in journal (Refereed)
  • 43.
    Ghebresus, Awet Ambesaghir
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences. Division for Clinical Pharmacology,Department of Laboratory Medicine, Karolinska Institutet .
    Pharmacodynamic, Pharmacokinetic and Pharmacogenetic Studies of Nandrolone Decanoate2015Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    Introduction: Nandrolone is one of the most abused androgenic anabolic steroid. Nandrolone is, inside the body, primarily metabolized into 19-norandrosterone (19-NA) and 19-noretiocholanolone (19-NE). Nandrolone abuse has been shown to cause alterations in the lipid- and endocrine profile, also to induce endothelial dysfunction. The mechanisms behind the alterations in these endogenous substances are not known, but one might speculate that alteration in gene expression may partly play a role.

    Aim: To analyze how a single dose of nandrolone affect the oxidative stress, the cholesterol and endocrine profile in healthy volunteers, and to analyze the androgenic effect as determined by testosterone and LH/FS levels in relation to genetic variations, in order to increase the knowledge on nandrolone side effects in humans.

    Materials and Methods: Elevenhealthy subjects were included. Genotyping was done using TaqMan allelic discrimination method and quantitative PCR. Real-time PCR was conducted to quantify the gene expression of HMGCR and the SOD’s. The cholesterol profile and hormone levels were analyzed at the Division of Clinical Chemistry and the hematocrit profile were measured at the Anti-Doping Laboratory according to WADA’s technical document TD2014 BAR.

    Results: Several correlations between lipoproteins and hormones were found. The gene expression of HMGCR was induced but showed no correlation with other results. Significant alterations were found on the serum levels of LH, FSH, testosterone, total cholesterol, LDL, ApoB and SHBG. Association between UGT2B17 ins/del polymorphism and a slower decrease of serum testosterone showed significance. The hematocrit profile was not altered whereas an increase in lymphocyte count was noted.

    Conclusions: One single dose of nandrolone causes a perturbation in the blood lipid- and endocrine profile. Genetic polymorphism may partly affect the serum levels of testosterone post nandrolone administration.

  • 44.
    Gillespie, Thomas
    Emory University, Atlanta, GA, USA.
    24. Habitat Fragmentation and Species Barriers2012In: Ecology and Animal Health / [ed] Leif Norrgren and Jeffrey Levengood, Uppsala: Baltic University Press , 2012, 1, p. 199-200Chapter in book (Other (popular science, discussion, etc.))
  • 45. Griekspoor, Petra
    et al.
    Engvall, Eva Olsson
    Olsen, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases.
    Waldenström, Jonas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases.
    Multilocus sequence typing of Campylobacter jejuni from broilers2010In: Veterinary Microbiology, ISSN 0378-1135, E-ISSN 1873-2542, Vol. 140, no 1-2, p. 180-185Article in journal (Refereed)
    Abstract [en]

    Campylobacter jejuni isolates from a national Swedish Campylobacter monitoring in broilers were characterized by multilocus sequencing typing (MLST) in order to study the genetic diversity of this bacterial population. Isolates were initially characterized by pulsed-field gel electrophoresis (PFGE). One hundred were chosen for MLST genotyping. PFGE identified 69 distinct types compared to 44 different sequence types (STs) identified with MLST. Eighteen STs had not been described previously, while the remaining 26 STs were assigned to previously known clonal complexes. The majority of isolates were of genotypes noted in broilers and in humans in earlier studies. However, three clonal complexes, ST-206 complex, ST-677 complex and ST-1034 complex, previously associated with wild bird and environmental samples, were among the genotypes found. This study shows that most of the Swedish broiler isolates were of genotypes noted as common in broilers. However, it also highlights the potential influence of environmental sources on the broiler C jejuni genotypes. (C) 2009 Elsevier B.V. All rights reserved.

  • 46. Grubb, Tamara
    et al.
    Frendin, Jan H. M.
    Edner, Anna
    Funkquist, Pia
    Hedenstierna, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Nyman, Gorel
    The effects of pulse-delivered inhaled nitric oxide on arterial oxygenation, ventilation-perfusion distribution and plasma endothelin-1 concentration in laterally recumbent isoflurane-anaesthetized horses2013In: Veterinary Anaesthesia and Analgesia, ISSN 1467-2987, E-ISSN 1467-2995, Vol. 40, no 6, p. E19-E30Article in journal (Refereed)
    Abstract [en]

    Objectives Anaesthetized horses commonly become hypoxaemic due to ventilation/perfusion ((V) over dot(A)/(Q) over dot) mismatch and increased pulmonary shunt fraction ((Q) over dots/(Q) over dott). Pulse-delivered inhaled nitric oxide may improve oxygenation but may increase plasma concentration of the potent vasoconstrictor, endothelin-1 (ET-1). Objectives: Study 1) compare arterial oxygen concentration (PaO2) and saturation (SaO(2)), calculated ((Q) over dots/(Q) over dott) and ET-1 concentration; and Study 2) assess ((V) over dot(A)/(Q) over dot) matching and measured ((Q) over dots/(Q) over dott) in isoflurane-anaesthetized horses in left lateral recumbency receiving pulse-delivered inhaled nitric oxide (PiNO group) or inhalant gas only (C group). Study design Prospective research trial. Animals Ten Healthy adult Standardbred horses. Two horses were anaesthestized in both groups in a random cross-over design with >4 weeks between studies. Methods Study 1) Cardiopulmonary data including PaO2, SaO(2), ((Q) over dots/(Q) over dott) and ET-1 concentration were measured or calculated prior to and at various points during PiNO administration in 6PiNO and 6C horses. Two-way repeated measures ANOVA with Bonferroni significant difference test was used for data analysis with p < 0.05 considered significant. Study 2) ((V) over dot(A)/(Q) over dot) matching and ((Q) over dots/(Q) over dott) were determined using the multiple inert gas elimination technique in 3 horses. Data were collected after 60 minutes of anaesthesia without PiNO (baseline) and 15 minutes after PiNO was pulsed during the first 30%, and then the first 60%, of inspiration. Data were descriptive only. Results Study 1) PaO2 and SaO2 were higher and calculated ((Q) over dots/(Q) over dott) was lower in the PiNO group than the C group at most time points. ET-1 was not different over time or between groups. Study 2) ((V) over dot(A)/(Q) over dot) matching and measured ((Q) over dots/(Q) over dott) were improved from baseline in all horses but PiNO60% provided no improvement when compared to PiNO30%. Conclusions and Clinical Relevance PiNO delivered in the initial portion of the inspiration effectively relieves hypoxaemia in anaesthetized horses by improving ((V) over dot(A)/(Q) over dot) matching and decreasing ((Q) over dots/(Q) over dott) without affecting ET-1.

  • 47.
    Gunnarsson, Ulrika
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Kerje, Susanne
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Bed'hom, Bertrand
    Sahlqvist, Anna-Stina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Ekwall, Olov
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Tixier-Boichard, Michele
    Kämpe, Olle
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Andersson, Leif
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    The Dark brown plumage color in chickens is caused by an 8.3-kb deletion upstream of SOX102011In: Pigment Cell & Melanoma Research, ISSN 1755-1471, E-ISSN 1755-148X, Vol. 24, no 2, p. 268-274Article in journal (Other academic)
    Abstract [en]

    The Dark brown (DB) mutation in chickens reduces expression of black eumelanin and enhances expression of red pheomelanin, but only in certain parts of the plumage. Here, we present genetic evidence that an 8.3-kb deletion upstream of the SOX10 transcription start site is the causal mutation underlying the DB phenotype. The SOX10 transcription factor has a well-established role in melanocyte biology and is essential for melanocyte migration and survival. Previous studies have demonstrated that the mouse homolog of a highly conserved element within the deleted region is a SOX10 enhancer. The mechanism of action of this mutation remains to be established, but one possible scenario is that the deletion leads to reduced SOX10 expression which in turn down-regulates expression of key enzymes in pigment synthesis such as tyrosinase. Lower tyrosinase activity leads to a shift toward a more pheomelanistic (reddish) plumage color, which is the characteristic feature of the DB phenotype.

  • 48.
    Hagelin, Joakim
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Comparative Medicine.
    Hau, J.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Comparative Medicine.
    Carlsson, Hans-Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Comparative Medicine.
    Attitude of Swedish veterinary and medical students to animal experimentation2000In: The Veterinary Record, ISSN 0042-4900, E-ISSN 2042-7670, Vol. 146, no 26, p. 757-760Article in journal (Refereed)
    Abstract [en]

    Nearly all veterinary and medical students (94 per cent) found it morally acceptable to use animals in research and believed it to be a necessity in order to treat human diseases. In contrast with the medical students a substantial proportion ofveterinary students (40 per cent) considered themselves animal rights activists. Unlike themedical curriculum, the veterinary curriculum contains a two-week course in laboratoryanimal medicine, and a higher proportion of the students who had not been through this course was opposed to the use of animals in research than of the students who had completed the course. The course modified the views of half the students; more than 26 per cent of them became more positive towards animal use in research after the courser whereas 3 per cent became more negative.

  • 49. Hagglund, Sara
    et al.
    Hu, Kefei
    Blodorn, Krister
    Makabi-Panzu, Boby
    Gaillard, Anne-Laure
    Ellencrona, Karin
    Chevret, Didier
    Hellman, Lars
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Chemical Biology.
    Bengtsson, Karin Lovgren
    Riffault, Sabine
    Taylor, Geraldine
    Valarcher, Jean Francois
    Eleouet, Jean-Francois
    Characterization of an Experimental Vaccine for Bovine Respiratory Syncytial Virus2014In: Clinical and Vaccine Immunology, ISSN 1556-6811, E-ISSN 1556-679X, Vol. 21, no 7, p. 997-1004Article in journal (Refereed)
    Abstract [en]

    Bovine respiratory syncytial virus (BRSV) and human respiratory syncytial virus (HRSV) are major causes of respiratory disease in calves and children, respectively, and are priorities for vaccine development. We previously demonstrated that an experimental vaccine, BRSV-immunostimulating complex (ISCOM), is effective in calves with maternal antibodies. The present study focuses on the antigenic characterization of this vaccine for the design of new-generation subunit vaccines. The results of our study confirmed the presence of membrane glycoprotein (G), fusion glycoprotein (F), and nucleoprotein (N) proteins in the ISCOMs, and this knowledge was extended by the identification of matrix (M), M2-1, phosphoprotein (P), small hydrophobic protein (SH) and of cellular membrane proteins, such as the integrins alpha(V)beta(1), alpha(V)beta(3), and alpha(3)beta(1). The quantity of the major protein F was 4- to 5-fold greater than that of N (similar to 77 mu g versus similar to 17 mu g/calf dose), whereas G, M, M2-1, P, and SH were likely present in smaller amounts. The polymerase (L), M2-2, nonstructural 1 (NS1), and NS2 proteins were not detected, suggesting that they are not essential for protection. Sera from the BRSV-ISCOM-immunized calves contained high titers of IgG antibody specific for F, G, N, and SH. Antibody responses against M and P were not detected; however, this does not exclude their role in protective T-cell responses. The absence of immunopathological effects of the cellular proteins, such as integrins, needs to be further confirmed, and their possible contribution to adjuvant functions requires elucidation. This work suggests that a combination of several surface and internal proteins should be included in subunit RSV vaccines and identifies absent proteins as potential candidates for differentiating infected from vaccinated animals.

  • 50.
    Hasan, Badrul
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Association between Hospital Waste and the House Crow (Corvus splendens) in the Dissemination of Antibiotic Resistance and the Epidemic Escherichia coli Clone O25b-ST131 in BangladeshManuscript (preprint) (Other academic)
    Abstract [en]

    Multiresistant bacteria constitute a serious health risk. In order to investigate the environmental contamination of antibiotic resistance in areas with poor waste management in Bangladesh, fecal samples from 238 house crows living in the surroundings of two major hospitals were screened for members of the Enterobacteriaceae family with extended spectrum beta-lactamase (ESBL)-production. These were compared with 31 ESBL-producing patient isolates, and the susceptibility of E. coli isolates was tested. Without selective pressure, 65.8% of the E. coli isolates from crows were resistant to one or more of 13 antibiotics, and 39.1% were multiresistant. The highest resistance rates were against tetracycline (52.2%), trimethoprim-sulphamethoxazole (43.5%), nalidixic acid (39.8%) and ampicillin (33.5% ). Fifty-nine percent of the crows were ESBL-carriers, and the isolates harbored CTX-M-1, CTX-M-15, CTX-M-55, CTX-M-79 or CTX-M-14-like genes. Two thirds of these ESBL-producers were multi-drug resistant. The ESBL-producing isolates from patients showed a higher rate of resistance compared with the ESBL-producers from crows. One hundred percent were multi-drug resistant, and most common was resistance to ciprofloxacin (93.3%) and trimethoprim-sulphamethoxazole (60%). The corresponding figures for ESBL-producing crow isolates were 41.3% and 57.3%. The crows and patients shared the epidemic E. coli clone O25b-ST131, which carried CTX-M-15 and CTX-M-14-like enzymes. Dissemination of ESBL-producing Klebsiella pneumoniae was also observed among the crows. In conclusion, the Bangladeshi house crow is the bird with the highest carriage rate of ESBL-producing bacteria observed so far. Their scavenging behavior at poorly managed hospital waste dumps, makes them into both reservoirs and active spreaders of antibiotic resistance into the environment. Nationwide programs are necessary to both improve the management of hospital waste and sewage and the control of the antibiotic usage to prevent further environmental contamination. 

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