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  • 301.
    Pelander, Lena
    et al.
    Department of Clinical Sciences, Swedish University of Agricultural Sciences, Uppsala, Sweden..
    Häggström, Jens
    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.
    Syme, Harriet
    Department of Clinical Science and Services, The Royal Veterinary College, Hertfordshire, United Kingdom.
    Elliott, Jonathan
    Department of Comparative Biomedical Sciences, The Royal Veterinary College, London, United Kingdom..
    Heiene, Reidun
    ABC Dyreklinikk Lillehammer AS, Hamarvegen 68A, 26 13 Lillehammer, Norway..
    Ljungvall, Ingrid
    Department of Clinical Sciences, Swedish University of Agricultural Sciences, Uppsala, Sweden..
    Comparison of the diagnostic value of symmetric dimethylarginine, cystatin C, and creatinine for detection of decreased glomerular filtration rate in dogs2019In: Journal of Veterinary Internal Medicine, ISSN 0891-6640, E-ISSN 1939-1676, Vol. 33, no 2, p. 630-639Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Early detection of decreased glomerular filtration rate (GFR) in dogs is challenging. Current methods are insensitive and new biomarkers are required.

    OBJECTIVE: To compare overall diagnostic performance of serum symmetric dimethylarginine (SDMA) and serum cystatin C to serum creatinine, for detection of decreased GFR in clinically stable dogs, with or without chronic kidney disease (CKD).

    ANIMALS: Ninety-seven client-owned dogs: 67 dogs with a diagnosis or suspicion of CKD and 30 healthy dogs were prospectively included.

    METHODS: Prospective diagnostic accuracy study. All dogs underwent physical examination, systemic arterial blood pressure measurement, urinalysis, hematology and blood biochemistry analysis, cardiac and urinary ultrasound examinations, and scintigraphy for estimation of glomerular filtration rate (mGFR). Frozen serum was used for batch analysis of SDMA and cystatin C.

    RESULTS: The area under the curve of creatinine, SDMA, and cystatin C for detection of an mGFR <30.8 mL/min/L was 0.98 (95% confidence interval [CI], 0.93-1.0), 0.96 (95% CI, 0.91-0.99), and 0.87 (95% CI, 0.79-0.93), respectively. The sensitivity of both creatinine and SDMA at their prespecified cutoffs (115 μmol/L [1.3 mg/dL] and 14 μg/dL) for detection of an abnormal mGFR was 90%. The specificity was 90% for creatinine and 87% for SDMA. When adjusting the cutoff for cystatin C to correspond to a diagnostic sensitivity of 90% (0.49 mg/L), specificity was lower (72%) than that of creatinine and SDMA.

    CONCLUSIONS AND CLINICAL IMPORTANCE: Overall diagnostic performance of creatinine and SDMA for detection of decreased mGFR was similar. Overall diagnostic performance of cystatin C was inferior to both creatinine and SDMA.

  • 302. Perez-Cornago, Aurora
    et al.
    Appleby, Paul N.
    Pischon, Tobias
    Tsilidis, Konstantinos K.
    Tjonneland, Anne
    Olsen, Anja
    Overvad, Kim
    Kaaks, Rudolf
    Kuehn, Tilman
    Boeing, Heiner
    Steffen, Annika
    Trichopoulou, Antonia
    Lagiou, Pagona
    Kritikou, Maria
    Krogh, Vittorio
    Palli, Domenico
    Sacerdote, Carlotta
    Tumino, Rosario
    Bueno-de-Mesquita, H. Bas
    Agudo, Antonio
    Larranaga, Nerea
    Molina-Portillo, Elena
    Barricarte, Aurelio
    Chirlaque, Maria-Dolores
    Ramon Quiros, J.
    Stattin, Pär
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology. Department of Surgical Sciences, Uppsala University.
    Häggström, Christel
    Umeå University, Faculty of Medicine, Department of Biobank Research. Department of Surgical Sciences, Uppsala University.
    Wareham, Nick
    Khaw, Kay-Tee
    Schmidt, Julie A.
    Gunter, Marc
    Freisling, Heinz
    Aune, Dagfinn
    Ward, Heather
    Riboli, Elio
    Key, Timothy J.
    Travis, Ruth C.
    Tall height and obesity are associated with an increased risk of aggressive prostate cancer: results from the EPIC cohort study2017In: BMC Medicine, ISSN 1741-7015, E-ISSN 1741-7015, Vol. 15, article id 115Article in journal (Refereed)
    Abstract [en]

    Background: The relationship between body size and prostate cancer risk, and in particular risk by tumour characteristics, is not clear because most studies have not differentiated between high-grade or advanced stage tumours, but rather have assessed risk with a combined category of aggressive disease. We investigated the association of height and adiposity with incidence of and death from prostate cancer in 141,896 men in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Methods: Multivariable-adjusted Cox proportional hazards models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). After an average of 13.9 years of follow-up, there were 7024 incident prostate cancers and 934 prostate cancer deaths. Results: Height was not associated with total prostate cancer risk. Subgroup analyses showed heterogeneity in the association with height by tumour grade (P-heterogeneity = 0.002), with a positive association with risk for high-grade but not low-intermediate-grade disease (HR for high-grade disease tallest versus shortest fifth of height, 1.54; 95% CI, 1.18-2.03). Greater height was also associated with a higher risk for prostate cancer death (HR = 1.43, 1.14-1.80). Body mass index (BMI) was significantly inversely associated with total prostate cancer, but there was evidence of heterogeneity by tumour grade (P-heterogeneity = 0.01; HR = 0.89, 0.79-0.99 for low-intermediate grade and HR = 1.32, 1.01-1.72 for high-grade prostate cancer) and stage (P-heterogeneity = 0.01; HR = 0.86, 0.75-0.99 for localised stage and HR = 1.11, 0.92-1.33 for advanced stage). BMI was positively associated with prostate cancer death (HR = 1.35, 1.09-1.68). The results for waist circumference were generally similar to those for BMI, but the associations were slightly stronger for high-grade (HR = 1.43, 1.07-1.92) and fatal prostate cancer (HR = 1.55, 1.23-1.96). Conclusions: The findings from this large prospective study show that men who are taller and who have greater adiposity have an elevated risk of high-grade prostate cancer and prostate cancer death.

  • 303.
    Persson, Johanna
    University of Kalmar, School of Human Sciences.
    Hälsoundervisning: Elevers syn på hälsa inom ämnet Idrott och hälsa2009Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    Fler unga människor än någonsin är idag överviktiga och stress och stressrelaterade symptom drabbar idag allt fler unga. Därför är det viktigt att unga människor får kunskaper om hur de på bästa sätt kan ta hand om sig själva.

     Syftet med detta arbete är att undersöka hur elever som läser gymnasiets kurs Idrott och hälsa A ser på den hälsoundervisning de får.

    Detta är relevant för alla som arbetar som idrott och hälsa lärare för att kunna hitta en jämkning mellan kursplan och elevernas tankar och förkunskaper.

     Genom intervjuer och fokusintervjuer kom jag fram till att eleverna vill lära sig mer om stress och hur man hanterar stress samt om kost. Eleverna tycker däremot att idrottsläraren inte är rätt person att lära ut kunskaper om tobak.

  • 304.
    Peterson, Gunnel
    Linköping University, Department of Medical and Health Sciences, Division of Physiotherapy. Linköping University, Faculty of Medicine and Health Sciences.
    Neck muscle function in individuals with persistent pain and disability after whiplash injury2016Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Background: Neck pain and disability are common after whiplash injury. One year after the accident up to 50 % still have symptoms called whiplash associated disorders (WAD). Despite decades of research the cause of persistent pain and disability are largely unknown and effective treatment and diagnostic tools are lacking. Altered neck muscle function may cause pain and disability, and real-time non-invasive methods that investigate both superficial and deep neck muscle function need to be evaluated.

    Aim: The general aim of the work presented in this thesis was to investigate mechanical neck muscle function and evaluate effects of three different exercise interventions related to neck muscle function in individuals with persistent pain and disability after whiplash injury.

    Method: The thesis comprised two studies, reported in four papers. Study A was a prospective randomized controlled trail with 216 participants. The effects of three exercise interventions; neck-specific exercises, neck-specific exercises with behavioral approach and prescription of physical activity were evaluated. Neck muscle endurance, perceived pain following testing, kinesiophobia and satisfaction with treatment were compared between the three groups (paper I). Study B was an experimental case-control study with participants consecutively recruited from the randomized controlled trial. Deformation and deformation rates in the neck muscles were investigated with real-time ultrasound imaging during ten repetitive arm elevations (paper II-IV). To investigate ventral neck muscles, 26 individuals with WAD were compared with 26 healthy controls (paper II). The dorsal neck muscles were investigated in paper III, including 40 individuals with WAD and 40 controls. In total 46 individuals, 23 with WAD and 23 healthy controls were included in paper IV to develop ventral neck muscle interaction models.

    Results: Paper I: Participants in the two neck-specific exercise groups (with and without behavioral approach) showed increased dorsal neck muscle endurance (p = 0.003), decreased pain intensity following testing (p = 0.04) and were more satisfied with treatment (p < 0.001) than participants in the prescribed physical activity group. Kinesiophobia did not significantly differ between groups (p > 0.12).

    Paper II: Deformation and deformation rate showed linear positive relationship between ventral muscle pairs in healthy controls, especially between superficial and deep neck muscles. This relationship was weaker or absent in the WAD group.

    Paper III: The WAD group had higher deformation rates in the deepest dorsal neck muscles during the first and tenth (only women) arm elevations compared to the control group (p < 0.04). Women in the WAD group showed a weaker linear relationship between the two deepest dorsal neck muscles compared to women in the control group.

    Paper IV: The results revealed two different ventral neck muscle models in individuals with WAD and healthy controls (R2Y = 0.72, Q2Y = 0.59). The models were capable to detect different neck muscle interplay in people with WAD.

    Conclusion: Neck-specific exercise intervention with or without a behavioral approach appears to improve neck muscle endurance in individuals with persistent WAD. Decreased pain after the neck muscle endurance test also suggests improved tolerance of load in these two groups. Altered mechanical neck muscle function was revealed in individuals with WAD indicating decreased muscular support for maintain a stable cervical spine during repetitive arm elevations. The results show great promise for improved diagnosis of neck muscle function in WAD.

  • 305.
    Pettigrew, James E.
    et al.
    University of Illinois at Urbana-Champaign.
    Baker, Rodney B.
    North Carolina State University, Raleigh, NC, USA.
    27. Health Management with Reduced Use of Antibiotics in Pig Production2012In: Ecology and Animal Health / [ed] Leif Norrgren and Jeffrey Levengood, Uppsala: Baltic University Press , 2012, 1, p. 214-221Chapter in book (Other (popular science, discussion, etc.))
  • 306. Pfeffer, Martin
    et al.
    Modlmaier, Michael
    Lundström, Jan O.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Population and Conservation Biology.
    Lack of Evidence for the Presence of Mosquito-Borne Arboviruses in the Upper Rhine Valley, Germany, in 1999 to 20002010In: Journal of Clinical Microbiology, ISSN 0095-1137, E-ISSN 1098-660X, Vol. 48, no 9, p. 3457-3458Article in journal (Refereed)
  • 307.
    Piehl, Lidia L
    et al.
    Cátedra de Física and Instituto de Bioquímica y Medicina Molecular, IBIMOL (UBA-CONICET), Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Buenos Aires, Argentina.
    Fischman, M Laura
    Laboratorio de Calidad Seminal y Criopreservación de Gametas, Cátedra de Física Biológica, INITRA, Facultad de Ciencias Veterinarias, Universidad de Buenos Aires, Buenos Aires, Argentina.
    Hellman, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Ludwig Institute for Cancer Research.
    Cisale, Humberto
    Laboratorio de Calidad Seminal y Criopreservación de Gametas, Cátedra de Física Biológica, INITRA, Facultad de Ciencias Veterinarias, Universidad de Buenos Aires, Buenos Aires, Argentina.
    Miranda, Patricia V
    Instituto de Biología y Medicina Experimental-CONICET, Buenos Aires, Argentina.
    Boar seminal plasma exosomes: Effect on sperm function and protein identification by sequencing.2013In: Theriogenology, ISSN 0093-691X, E-ISSN 1879-3231, Vol. 79, no 7, p. 1071-1082Article in journal (Refereed)
    Abstract [en]

    Mammalian seminal plasma contains membranous vesicles (exosomes), with a high content of cholesterol and sphingomyelin and a complex protein composition. Their physiological role is uncertain because sperm stabilization and activation effects have been reported. To analyze a putative modulatory role for semen exosomes on sperm activity in the boar, the effects of these vesicles on several sperm functional parameters were examined. Additionally, boar exosome proteins were sequenced and their incorporation into sperm was explored. Boar sperm were incubated under conditions that induce capacitation, manifested as increased tyrosine phosphorylation, cholesterol loss and greater fluidity in apical membranes, and the ability to undergo the lysophosphatidylcholine-induced acrosome reaction. After establishing this cluster of capacitation-dependent functional parameters, the effect produced by exosomes when present during or after sperm capacitation was analyzed. Exosomes inhibited the capacitation-dependent cholesterol efflux and fluidity increase in apical membranes, and the disappearance of a 14-kD phosphorylated polypeptide. In contrast, the acrosome reaction (spontaneous and lysophosphatidylcholine-induced) was not affected, and sperm binding to the oocyte zona pellucida was reduced only when vesicles were present during gamete coincubation. Liposomes with a lipid composition similar to that present in exosomes mimicked these effects, except the one on zona pellucida binding. Interaction between exosomes and sperm was confirmed by transfer of aminopeptidase activity. In addition, the major exosome protein, identified as actin, appeared to associate with sperm after coincubation. Exosome composition had a predominance for structural proteins (actin, plastin, ezrin, and condensin), enzymes, and several porcine seminal plasma-specific polypeptides (e.g., spermadhesins). Transfer of proteins from exosome to sperm and their ability to block cholesterol efflux supports a direct interaction between these vesicles and sperm, whereas inhibition of some capacitation-dependent features suggests a stabilizing function for exosomes in boar semen.

  • 308.
    Pujato, N.
    et al.
    Univ Nacl Litoral, Fac Bioquim & Ciencias Biol, Santa Fe, Argentina.
    Camussone, C. M.
    Consejo Nacl Invest Cient & Tecn, Consejo Nacl Invest Cient & Tecn, Buenos Aires, DF, Argentina;INTA, Estn Expt Agr Rafaela, Santa Fe, Argentina.
    Renna, M. S.
    Consejo Nacl Invest Cient & Tecn, Consejo Nacl Invest Cient & Tecn, Buenos Aires, DF, Argentina;Univ Nacl Litoral, Fac Ciencias Vet, Esperanza, Santa Fe, Argentina.
    Perrig, M. S.
    Univ Nacl Litoral, Fac Bioquim & Ciencias Biol, Santa Fe, Argentina;Consejo Nacl Invest Cient & Tecn, Consejo Nacl Invest Cient & Tecn, Buenos Aires, DF, Argentina.
    Morein, B.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology and Infectious Medicine, Clinical Virology.
    Calvinho, L. F.
    INTA, Estn Expt Agr Rafaela, Santa Fe, Argentina;Univ Nacl Litoral, Fac Ciencias Vet, Esperanza, Santa Fe, Argentina.
    Marcipar, I. S.
    Univ Nacl Litoral, Fac Bioquim & Ciencias Biol, Santa Fe, Argentina;Consejo Nacl Invest Cient & Tecn, Consejo Nacl Invest Cient & Tecn, Buenos Aires, DF, Argentina.
    Evaluation of the humoral immune response to a multicomponent recombinant vaccine against S-aureus in healthy pregnant heifers2018In: The Veterinary Journal, ISSN 1090-0233, E-ISSN 1532-2971, Vol. 235, p. 47-53Article in journal (Refereed)
    Abstract [en]

    Staphylococcus aureus is a worldwide pathogen that causes mastitis in dairy herds. Shortcomings in control programs have encouraged the development of vaccines against this pathogen. This study evaluated the vaccine candidate VacR, which included recombinant S. aureus protein clumping factor A (rClf), fibronectin binding protein A (rFnBP) and hemolysin beta (rBt), formulated with a novel immune-stimulating complex. Comparisons were made between healthy pregnant heifers that received either VacR (n = 8; VacR group) or phosphate buffered saline (PBS) plus adjuvant (control group) SC in the supramammary lymph node area on days 45 and 15 before the expected calving date. Blood and foremilk samples were collected from 7 to 60 days post-calving. After calving, heifers in the VacR group produced higher total IgG (IgG(total)) titers against each component, in both serum (rBt, 3.4 x 10(5); rClf, 3.1 x 10(5); rFnBP, 2.3 x 10(5)) and milk (rBt, 2.6 x 10(4); rClf, 1.3 x 10(4); rFnBP, 1.1 x 10(4)), than control heifers (P < 0.0001). There were increased concentrations of IgG(1), and IgG(2) in VacR group (P < 0.05), in both serum and milk. Humoral responses remained high throughout the period most susceptible to intramammary infections (P < 0.01). Antibodies produced against S. aureus rClf and rFnBP reduced bacterial adherence to fibronectin and fibrinogen by 73% and 67%, respectively (P < 0.001). Milk antibodies against these adhesins inhibited S. aureus invasion of a mammary epithelial cell line (MAC-T), resulting in 15.7% of bacteria internalized (P < 0.0001). There was an approximately 6-fold reduction in the hemolysis titer for the native hemolysin in the VacR group compared to the control group (P < 0.0001) and a significantly increase in the proportion of positive neutrophils (VacR, 29.7%; PBS, 13.1%) and the mean fluorescent index (VacR, 217.4; PBS, 152.6; P < 0.01) in the VacR group. The results suggest that VacR is a valuable vaccine candidate against S. aureus infections, and merits further field trials and experimental challenges. (C) 2018 Elsevier Ltd. All rights reserved.

  • 309.
    Rahman, Mozibur
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    Effects of neuroactive steroids on the recombinant GABAA receptor in Xenopus oocyte2007Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Introduction: Neuroactive steroids represent a class of both synthetic and naturally occurring steroids that have an effect on neural function. In addition to classical genomic mechanism by the hormones progesterone, deoxycorticosterone and testosterone 3α-OH metabolites of these hormones enhance GABAA receptor through rapid non-genomic mechanism. The site(s) of action of these neuroactive steroids namely 3α-OH-5α-pregnan-20 one, (3α,5α)-3,21-deoxycorticosterone(3α5α-THDOC) and 5α androstane-3α,17β-diol on GABAA receptor are distinct from that of benzodiazepines and barbiturate binding sites. The modulation site(s) has a well-defined structure activity relationship with a 3α-hydroxy and a 20-ketone configuration in the pregnane molecule required for agonistic action. Pregnenolone sulfate is a noncompetitive GABAA receptor antagonist and inhibit GABA activated Cl- current in an activation dependant manner. 3β-hydroxy A-ring reduced pregnane steroids are also GABAA receptor antagonist and inhibit GABAA receptor function and its potentiation induced by their 3α-diesteromers in a noncompetitive manner.

    Aim: The aim was to investigate if the effect of GABA, pentobarbital antagonism by bicuculline and if the effect of GABA-agonist and antagonist neuroactive steroids including pregnenolone sulfate is dependant on the α-subunits of GABAA receptor. Furthermore, the studies aimed at investigating the binding site of pregnenolone sulfate and if its effect is dependent on γ-subunit. In addition, the inhibitory effect of pregnenolone sulfate and 3β-hydroxy steroids has been characterized. We also wanted to investigate if the neuroactive steroids effect vary between the human and rat recombinant α1β2γ2L receptors and between the long (L) and short (S) variants of γ2-subunit.

    Method: Experiments were performed by the two electrodes voltage-clamp technique using oocytes of Xenopus laevis expressed with recombinant GABAA receptors containing α1, α4 or α5, β2, γ2L and γ2S-subunits.

    Results: There was no difference between the α1, α4 and α5-containing subunits regarding GABA and pentobarbital inhibition by bicuculline. GABA-activated current in the binary αβ was potent than that of ternary αβγ receptor. Unlike Zn2+ effect, inhibition by pregnenolone sulfate on the GABAA receptor is not dependant on the γ-subunit. It is likely that the 2’ residue closest to the N-terminus of the protein at M2 helix on both α1 and β2 subunit are critical to the inhibitory actions of PS and the function of Cl- channels. Point mutation at M2 helix of the β2-subunit (b2A252S) can dramatically reduce the inhibitory effect of PS on the GABAA receptors without affecting the inhibitory properties of 3β-hydroxysteroids. Agonist and antagonist steroids also varied in their efficacy between the human and rat α1β2γ2L receptor. Neuroactive steroids also showed difference between human γ2L and γ2S-containing receptor.

    Conclusions: GABA and pentobarbital antagonism by bicuculline is not dependant on α-subunit. Pregnenolone sulfate binding site is different from that of Zn2+. 3β-hydroxysteroids and pregnenolone sulfate inhibit GABAA receptor through different mechanisms. Neuroactive steroids also differ between species and between the long and short variant of γ- subunit.

  • 310.
    Redmalm, David
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Sociology. Örebro universitet, Institutionen för humaniora, utbildnings- och samhällsvetenskap.
    Djur i bur även i hyllade djurparker2012In: Djurens Rätt, ISSN 0345-2409, no 1, p. 36-37Article in journal (Other (popular science, discussion, etc.))
  • 311.
    Renström, Frida
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Fat cell insulin resistance: an experimental study focusing on molecular mechanisms in type 2 diabetes2007Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The aim of the present thesis was to further increase our understanding of mechanisms contributing to and maintaining cellular insulin resistance in type 2 diabetes (T2D). For this reason, the effects of high glucose and insulin levels on glucose transport capacity and insulin signaling, with emphasis on insulin receptor substrate 1 (IRS-1) were assessed in fat cells. Altered levels of IRS-1 have previously been observed in adipose tissue from insulin-resistant and T2D subjects.

    A high glucose level (≥15 mM) for 24 h exerted only a minor impairment on glucose transport capacity in human adipocytes, as opposed to rat adipocytes. However, when combined with a high insulin level (104 µU/ml), basal and insulin-stimulated glucose transport was significantly impaired in both human and rat adipocytes. This was associated with a depletion of IRS-1 and IRS-2 protein levels in rat adipocytes, as a result of post-translational changes and altered gene transcription, respectively. In human adipocytes was only IRS-1 protein levels reduced. The high glucose/high insulin setting achieved maximal impairment of glucose transport within 6 h. Subsequent incubations of rat adipocytes under physiological conditions could partially restore insulin sensitivity. Interestingly, in both human and rat fat cells, decreased levels of IRSs occurred after the establishment of impaired glucose transport, suggesting that the observed depletion of IRSs is a consequence rather than a cause of insulin resistance. Nonetheless, IRS depletion is likely to further aggravate insulin resistance.

    Tyrosine phosphorylation of IRS-1 upon insulin stimulation activates the signaling pathway that mediates glucose transport. Pre-treatment of human adipocytes with high glucose and insulin levels was not associated with any alterations in the total IRS-1 Tyr612 phosphorylation following 10 min insulin stimulation. However, a significant increase in basal Tyr612 phosphorylation was observed. Furthermore, a rise in basal IRS-1 Ser312 phosphorylation was found. This is associated with reduced IRS-1 function and is considered to target IRS-1 to degradation pathways, and thus could potentially explain the observed decrease in IRS-1 protein levels. Our results imply an enhanced activation of insulin’s negative-feedback control mechanism that inhibit IRS-1 function. This could potentially have contributed to the observed impairment of insulin action on glucose transport in these cells. Accordingly, we have also shown that the downstream activation of protein kinase B upon insulin-stimulation is significantly impaired in human adipocytes exposed to the high glucose/high insulin setting, indicating a defect in the signaling pathway mediating glucose transport.

    We also investigated whether there are humoral factors in the circulation of T2D patients that contribute to peripheral insulin resistance. Human adipocytes cultured for 24 h in medium supplemented with 25% serum from T2D subjects, as compared to serum from non-diabetic subjects, displayed significantly reduced insulin-stimulated glucose uptake capacity. The effect could neither be attributed to glucose, insulin, FFA, TNF-α or IL-6 levels in the serum, but other circulating factor(s) seem to be of importance.

    In conclusion, chronic conditions of elevated glucose and/or insulin levels all impair insulin action on glucose turnover, but to different extents. A clear distinction between rat and human fat cells in the response to these different milieus was also observed. Alterations in the function of the key insulin signaling protein IRS-1 might be involved in the mechanisms underlying the impaired glucose uptake capacity. IRS-1 reduction however, occurs after but probably aggravates the existing insulin resistance. The effects of high glucose and/or insulin levels may be of importance in T2D, but additional novel factors present in the circulation of T2D patients seem to contribute to cellular insulin resistance.

  • 312. Riihimäki, Miia
    et al.
    Raine, Amanda
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology.
    Elfman, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Occupational and Environmental Medicine.
    Pringle, John
    Markers of respiratory inflammation in horses in relation to seasonal changes in air quality in a conventional racing stable2008In: Canadian Journal of Veterinary Research-Revue Canadienne de Recherche Veterinaire, ISSN 0830-9000, Vol. 72, no 5, p. 432-439Article in journal (Refereed)
    Abstract [en]

    Airborne factors in a conventionally managed racing stable and markers of pulmonary inflammation in the stabled horses were investigated on 3 occasions at 6-month intervals, including 2 winter periods and the intervening summer period. The stable measurements included inside and outside ambient temperature and relative humidity, levels of total and respirable dust, endotoxin, and 1,3-beta-glucan. Horses (n = 12) were examined in detail clinically as well as by endoscopy, bronchoalveolar lavage (BAL) cytology, and real-time polymerase chain reaction (RT-PCR) analysis of BAL-cells for IL-6 and IL-10 mRNA. Indoor measurements showed low dust levels irrespective of season. Inhalable dust, as well as 1,3-beta-glucan, were higher during the winter stabling period, whereas endotoxin levels were higher during summer. Complete data from all sampling occasions to be used for further evaluation was obtained for only 8 of the horses. There was a trend for elevation of BAL neutrophils in the horses during winter stabling that coincided with a 3.7-fold increased expression of IL-6 mRNA in BAL cells (P = 0.014). Compared to summer sampling, IL-10 mRNA expression was significantly upregulated in only 1 of the winter sampling occasions, implicating influence on immune regulation by factor/s apart from seasonal differences. Our findings suggest up-regulation of innate immunity in the airways of stabled horses; in particular involving IL-6 in association with mild elevations in respirable dust, 1,3-beta-glucan, and/or cold ambient air. However, given that this study was observational, other unmeasured environmental factors associated with winter stabling need to be considered.

  • 313.
    Rising, Anna
    et al.
    Swedish Univ Agr Sci, Dept Anat Physiol & Biochem, S-75007 Uppsala, Sweden.;Karolinska Inst, Div Neurogeriatr, Ctr Alzheimer Res, Dept Neurobiol Care Sci & Soc NVS, S-14157 Huddinge, Sweden..
    Cederlund, Ella
    Karolinska Inst, Dept Med Biochem & Biophys MBB, S-17177 Stockholm, Sweden..
    Palmberg, Carina
    Karolinska Inst, Ctr Prote Karolinska PKKI, S-17177 Stockholm, Sweden..
    Uhlhorn, Henrik
    Natl Vet Inst SVA, Dept Pathol & Wildlife Dis, S-75189 Uppsala, Sweden..
    Gaunitz, Stefan
    Karolinska Inst, Div Neurogeriatr, Ctr Alzheimer Res, Dept Neurobiol Care Sci & Soc NVS, S-14157 Huddinge, Sweden..
    Nordling, Kerstin
    Karolinska Inst, Div Neurogeriatr, Ctr Alzheimer Res, Dept Neurobiol Care Sci & Soc NVS, S-14157 Huddinge, Sweden..
    Agren, Erik
    Natl Vet Inst SVA, Dept Pathol & Wildlife Dis, S-75189 Uppsala, Sweden..
    Ihse, Elisabet
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Westermark, Gunilla
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Tjernberg, Lars
    Karolinska Inst, Div Neurogeriatr, Ctr Alzheimer Res, Dept Neurobiol Care Sci & Soc NVS, S-14157 Huddinge, Sweden..
    Jornvall, Hans
    Karolinska Inst, Dept Med Biochem & Biophys MBB, S-17177 Stockholm, Sweden..
    Johansson, Jan
    Swedish Univ Agr Sci, Dept Anat Physiol & Biochem, S-75007 Uppsala, Sweden.;Karolinska Inst, Div Neurogeriatr, Ctr Alzheimer Res, Dept Neurobiol Care Sci & Soc NVS, S-14157 Huddinge, Sweden..
    Westermark, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Systemic AA amyloidosis in the red fox (Vulpes vulpes)2017In: Protein Science, ISSN 0961-8368, E-ISSN 1469-896X, Vol. 26, no 11, p. 2312-2318Article in journal (Refereed)
    Abstract [en]

    Amyloid A (AA) amyloidosis occurs spontaneously in many mammals and birds, but the prevalence varies considerably among different species, and even among subgroups of the same species. The Blue fox and the Gray fox seem to be resistant to the development of AA amyloidosis, while Island foxes have a high prevalence of the disease. Herein, we report on the identification of AA amyloidosis in the Red fox (Vulpes vulpes). Edman degradation and tandem MS analysis of proteolyzed amyloid protein revealed that the amyloid partly was composed of full-length SAA. Its amino acid sequence was determined and found to consist of 111 amino acid residues. Based on inter-species sequence comparisons we found four residue exchanges (Ser31, Lys63, Leu71, Lys72) between the Red and Blue fox SAAs. Lys63 seems unique to the Red fox SAA. We found no obvious explanation to how these exchanges might correlate with the reported differences in SAA amyloidogenicity. Furthermore, in contrast to fibrils from many other mammalian species, the isolated amyloid fibrils from Red fox did not seed AA amyloidosis in a mouse model.

  • 314.
    Roasto, Mati
    et al.
    Estonian University of Life Sciences, Tartu, Estonia.
    Hörman, Ari
    Estonian University of Life Sciences, Tartu, Estonia.
    Hänninen, Marja-Liisa
    University of Helsinki.
    26. Antimicrobial Resistance: a Food Safety Perspective2012In: Ecology and Animal Health / [ed] Leif Norrgren and Jeffrey Levengood, Uppsala: Baltic University Press , 2012, 2, p. 212-213Chapter in book (Other (popular science, discussion, etc.))
  • 315.
    Roca, J.
    et al.
    University of Murcia, Spain.
    Parrilla, I.
    University of Murcia, Spain.
    Gil, M. A.
    University of Murcia, Spain.
    Cuello, C.
    University of Murcia, Spain.
    Martinez, E. A.
    University of Murcia, Spain.
    Rodriguez-Martinez, Heriberto
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Non-viable sperm in the ejaculate: Lethal escorts for Contemporary viable sperm2016In: Animal Reproduction Science, ISSN 0378-4320, E-ISSN 1873-2232, Vol. 169, p. 24-31Article in journal (Refereed)
    Abstract [en]

    Non-viable sperm ("dead sperm") are present invariable numbers in mammalian ejaculates and their number increase substantially when semen is stored, particularly cryopreserved. This review comparatively highlights, with experimental data in porcine, the role-played by non-viable sperm in the outcome of semen used in assisted reproductive technologies. As well, the review discusses our current understanding of their origin and the pathways involved when their large numbers negative influence the functional lifespan of contemporary viable sperm to eventually cause irreversible dysfunction that reduces their fertility potential and their ability to develop healthy embryos. Finally, it highlights procedures currently available to mitigate these harmful effects. (C) 2016 Elsevier B.V. All rights reserved.

  • 316.
    Rodriguez-Martinez, Heriberto
    Linköping University, Department of Clinical and Experimental Medicine, Developmental Biology. Linköping University, Faculty of Health Sciences.
    Livestock semen biotechnology and management2012In: Encyclopedia of Life Support Systems (EOLSS): Animal Reproduction in Livestock / [ed] S Astiz Blanco & A Gonzalez Bulnes, Oxford, UK: Eolss Publishers, UNESCO , 2012, 1:a, p. 1-14Chapter in book (Other academic)
    Abstract [en]

    Modern livestock breeding is basically dependent on the proper use of semen for artificial insemination of females and of other reproductive biotechnologies such as the production of embryos in vitro for embryo transfer. Both these techniques have made possible not only the wide dissemination of genetic material onto breeding populations but also enhanced the selection of best sires, owing to the development of better diagnostic techniques for sperm function and of preservation of seminal material over time. Although use of liquid semen cooled to room temperature, to intermediate temperatures (+16-20°C) or chilled (+5°C) dominates in some livestock species (swine respectively small ruminants), cryopreservation is rule in bovine and it is advancing in other species by the design of new containers, freezing methods and the use of better insemination strategies. Reliable semen diagnostics is absolutely essential to disclose which semen is to be processed/cryopreserved but also to aim determination  of a potential fertilizing capacity in the laboratory, thus saving costs prior to artificial insemination. However, there is a yet no single laboratory method that accurately prognoses fertility in livestock, requiring use of a battery of diagnostic methods. Novel techniques for optimal use of ejaculates (low-dose) and intrauterine deposition of semen throughout species are those management techniques that shall increase our capabilities for better diagnostics/selection of semen/male potential fertility, of cryopreservation techniques and a more rational dissemination of genetics.

  • 317.
    Rohdin, C.
    et al.
    Swedish Univ Agr Sci, Dept Clin Sci, S-75007 Uppsala, Sweden;Albano Small Anim Hosp, Anicura, Rinkebyvagen 21, S-18236 Danderyd, Sweden.
    Haggstrom, J.
    Swedish Univ Agr Sci, Dept Clin Sci, S-75007 Uppsala, Sweden.
    Ljungvall, I.
    Swedish Univ Agr Sci, Dept Clin Sci, S-75007 Uppsala, Sweden.
    Lee, H. Nyman
    Bagarmossen Small Anim Hosp, Anicura, Ljusnevagen 17, S-12848 Bagarmossen, Sweden.
    De Decker, S.
    Univ London, Royal Vet Coll, Clin Sci & Serv, Hawkshead Lane, N Mymms AL9 7TA, England.
    Bertram, S.
    Univ London, Royal Vet Coll, Clin Sci & Serv, Hawkshead Lane, N Mymms AL9 7TA, England.
    Lindblad-Toh, Kerstin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Uppsala University, Science for Life Laboratory, SciLifeLab. Broad Inst Harvard & MIT, Cambridge, MA USA.
    Jaderlund, K. Hultin
    Norwegian Univ Life Sci, Dept Compan Anim Clin Sci, N-0033 Oslo, Norway.
    Presence of thoracic and lumbar vertebral malformations in pugs with and without chronic neurological deficits2018In: The Veterinary Journal, ISSN 1090-0233, E-ISSN 1532-2971, Vol. 241, p. 24-30Article in journal (Refereed)
    Abstract [en]

    Congenital vertebral malformations (CVMs) are common in brachycephalic dogs such as the pug, and are often considered incidental findings. However, specific CVMs have been suggested to be associated with neurological deficits in pugs. The objective of this study was to investigate the clinical importance of CVMs in the pug by comparing computed tomography studies of the thoracolumbar spine from pugs without neurological deficits with those from pugs with a confirmed T3-L3 spinal cord lesion and neurological deficits consistent with a chronic T3-L3 myelopathy. A total of 57 pugs were recruited into the study from Sweden (n=33), United Kingdom (n=21) and Norway (n = 3); 30 with neurological deficits and 27 without. Focal T3-L3 pathology was confirmed in all pugs with neurological deficits by magnetic resonance imaging (n = 29) and/or pathology (n = 15). Computed tomography studies of the thoracolumbar spine from pugs with and without neurological deficits were compared to investigate possible associations between presentation of neurological deficits consistent with chronic T3-L3 pathology and signalment variables, presence of CVMs and type of CVMs. Congenital vertebral malformations were as common in pugs with, as in pugs without, neurological deficits. Regardless of neurological status, the majority of pugs (96%) presented with one or more CVM. An association between presence, or type of CVM in the T1-L3 vertebral column, and neurological deficits consistent with T3-L3 pathology could not be confirmed.

  • 318.
    Rohdin, Cecilia
    et al.
    Swedish Univ Agr Sci, Dept Clin Sci, Uppsala, Sweden.;Albano Anim Hosp, Anicura, Danderyd, Sweden..
    Jäderlund, Karin Hultin
    Norwegian Univ Life Sci, Dept Compan Anim Clin Sci, Oslo, Norway..
    Ljungvall, Ingrid
    Swedish Univ Agr Sci, Dept Clin Sci, 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 Harvard & Massachusetts, Inst Technol, Cambridge, MA USA..
    Häggstrom, Jens
    Swedish Univ Agr Sci, Dept Clin Sci, Uppsala, Sweden..
    High prevalence of gait abnormalities in pugs2018In: The Veterinary Record, ISSN 0042-4900, E-ISSN 2042-7670, Vol. 182, no 6, article id 167Article in journal (Refereed)
    Abstract [en]

    The objective of this prospective study was to determine the prevalence of gait abnormalities in a cohort of Swedish pugs by using an owner-based questionnaire targeting signs of gait abnormality and video footage showing the dog's gait. This study also evaluated associated conditions of abnormal gait, including other health disorders prevalent in the breed. Five hundred and fifty (550) pugs registered in the Swedish Kennel Club, of one, five and eight years of age, in 2015 and 2016, were included in the study. Gait abnormalities were reported in 30.7 per cent of the responses. In the majority of cases, the character of the described gait indicated a neurological cause for the gait abnormality. An association was observed between abnormal gait and age, with gait abnormalities being significantly more common in older pugs (P=0.004). An association was also found between abnormal gait and dyspnoea, with dyspnoea being significantly more common in pugs with gait abnormalities (P<0.0001). This study demonstrated that the prevalence of gait abnormalities was high in the Swedish pug breed and increased with age. Future studies on the mechanisms behind these gait abnormalities are warranted.

  • 319. Rungelrath, Viktoria
    et al.
    Wohlsein, Jan Christian
    Siebert, Ursula
    Stott, Jeffrey
    Prenger-Berninghoff, Ellen
    von Pawel-Rammingen, Ulrich
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine). Umeå University, Faculty of Medicine, Umeå Centre for Microbial Research (UCMR).
    Valentin-Weigand, Peter
    Baums, Christoph G.
    Seele, Jana
    Identification of a novel host-specific IgG protease in Streptococcus phocae subsp phocae2017In: Veterinary Microbiology, ISSN 0378-1135, E-ISSN 1873-2542, Vol. 201, p. 42-48Article in journal (Refereed)
    Abstract [en]

    Streptococcus (S.) phocae subsp. phocae causes bronchopneumonia and septicemia in a variety of marine mammals. Especially in harbor seals infected with phocine distemper virus it plays an important role as an opportunistic pathogen. This study was initiated by the detection of IgG cleavage products in Western blot analysis after incubation of bacterial supernatant with harbor seal serum. Hence, the objectives of this study were the identification and characterization of a secreted IgG cleaving protease in S. phocae subsp. phocae isolated from marine mammals. To further identify the responsible factor of IgG cleavage a protease inhibitor profile was generated. Inhibition of the IgG cleaving activity by iodoacetamide and Z-LVG-CHN2 indicated that a cysteine protease is involved. Moreover, an anti-IdeS antibody directed against the IgG endopeptidase IdeS of S. pyogenes showed cross reactivity with the putative IgG protease of S. phocae subsp. phocae. The IgG cleaving factor of S. phocae subsp. phocae was identified through an inverse PCR approach and designated IdeP (Immunoglobulin G degrading enzyme of S. phocae subsp. phocae) in analogy to the cysteine protease IdeS. Notably, recombinant (r) IdeP is a host and substrate specific protease as it cleaves IgG from grey and harbor seals but not IgG from harbor porpoises or non-marine mammals. The identification of IdeP represents the first description of a protein in S. phocae subsp. phocae involved in immune evasion. Furthermore, the fact that IdeP cleaves solely IgG of certain marine mammals reflects functional adaption of S. phocae subsp. phocae to grey and harbor seals as its main hosts.

  • 320.
    Sahlin, Kent
    et al.
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences.
    Nielsen, Jens Steen
    Mogensen, Martin
    Tonkonogi, Michail
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences.
    Repeated static contractions increase mitochondrial vulnerability towards oxidative stress in human skeletal muscle2007In: Journal of applied physiology, ISSN 8750-7587, E-ISSN 1522-1601, Vol. 101, p. 833-839Article in journal (Refereed)
    Abstract [en]

    Repeated static contractions (RSC) induce large fluctuations in tissue oxygen tension and increase the generation of reactive oxygen species (ROS). This study investigated the effect of RSC on muscle contractility, mitochondrial respiratory function, and in vitro sarcoplasmatic reticulum (SR) Ca2+-kinetics in human muscle. Ten male subjects performed 5 bouts of static knee extension with 10 min rest in between. Each bout of RSC (target torque 66% of maximal voluntary contraction torque, MVC) was maintained to fatigue. Muscle biopsies were taken pre-exercise and 0.3 and 24 h post-exercise from vastus lateralis. Mitochondria were isolated and respiratory function measured after incubation with H2O2 (HPX) or control medium (CON). Mitochondrial function was not affected by RSC during CON. However, RSC exacerbated mitochondrial dysfunction during HPX resulting in decreased respiratory control index, decreased mitochondrial efficiency (P/O ratio) and increased non-coupled respiration (HPX/CON post vs. pre-exercise). SR Ca2+ uptake rate was lower 0.3 h vs. 24 h post-exercise, whereas SR Ca2+ release rate was unchanged. RSC resulted in long-lasting changes in muscle contractility including reduced maximal torque, low frequency fatigue (LFF) and faster torque relaxation. It is concluded that RSC increases mitochondrial vulnerability towards ROS, reduces SR Ca2+ uptake rate and causes LFF. Although conclusive evidence is lacking we suggest that these changes are related to increased formation of ROS during RSC.

  • 321.
    Salmon Hillbertz, Nicolette H. C.
    Department of Animal Breeding and Genetics, Swedish University of Agricultural Sciences.
    Inheritance of dermoid sinus in the Rhodesian ridgeback2005In: Journal of Small Animal Practice, ISSN 0022-4510, E-ISSN 1748-5827, Vol. 46, no 2, p. 71-4Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: TO define the mode of inheritance of dermoid sinus.

    METHODS: A chi-squared analysis was performed on data from 46 litters produced between 1990 and 2001. Data were corrected to avoid bias in the segregation ratio.

    RESULTS: In data from 57 litters (n=492), 82 dermoid sinus positive offspring were observed. The frequency of affected offspring in the Swedish Rhodesian ridgeback population is estimated to be between 8 and 10 per cent.

    CLINICAL SIGNIFICANCE: Bias in heredity pattern may be caused by undetected dermoid sinus type V. Improved clinical diagnosis of all dermoid sinus types is therefore crucial.

  • 322.
    Salomonsson, Matilda L.
    et al.
    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, SE-75189 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, SE-75189 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, SE-75189 Uppsala, Sweden.
    Quantification of dimethylsulfoxide (DMSO) in equine plasma and urine using HILIC-MS/MS2017In: Drug Testing and Analysis, ISSN 1942-7603, E-ISSN 1942-7611, Vol. 9, no 6, p. 935-941Article in journal (Refereed)
    Abstract [en]

    This paper describes quantitative methods for the determination of dimethylsulfoxide (DMSO) in equine plasma and urine based on simple precipitation and dilution followed by hydrophilic interaction liquid chromatography coupled to tandem mass spectrometry (HILIC-MS/MS). DMSO is a polar solvent with analgesic and anti-inflammatory properties. Its pharmacological features make it prohibited in horse racing. However, since DMSO is naturally present in the horses' environment, international threshold values have been implemented for plasma and urine (1 and 15 mu g/mL, respectively). Previously presented quantitative methods for the determination of DMSO are based on gas chromatography, thus demanding a tedious extraction step to transfer the analyte from the aqueous bodily fluid to an injectable organic solvent. The column used in the presented method was an Acquity BEH HILIC and the mobile phase was a mixture of ammonium acetate buffer and acetonitrile delivered as a gradient. Hexadeuterated DMSO (H-2(6)-DMSO) was used as the internal standard. Validation was performed in the range of the international thresholds concerning selectivity, carry-over, linearity, precision, accuracy, stability and inter-individual matrix variation. The results fulfilled the predefined criteria and the methods were considered fit for purpose. Successful applications on real equine doping control samples were carried out with determined DMSO concentrations exceeding the international thresholds.

  • 323.
    Sanchez Crespo, Alejandro
    Stockholm University, Faculty of Science, Medical Radiation Physics (together with KI).
    Novel computational methods for image analysis and quantification using position sensitive radiation detectors2005Doctoral thesis, monograph (Other academic)
    Abstract [en]

    The major advantage of position sensitive radiation detector systems lies in their ability to non invasively map the regional distribution of the emitted radiation in real-time. Three of such detector systems were studied in this thesis, gamma-cameras, positron cameras and CMOS image sensors. A number of physical factors associated to these detectors degrade the qualitative and quantitative properties of the obtained images. These blurring factors could be divided into two groups. The first group consists of the general degrading factors inherent to the physical interaction processes of radiation with matter, such as scatter and attenuation processes which are common to all three detectors The second group consists of specific factors inherent to the particular radiation detection properties of the used detector which have to be separately studied for each detector system. Therefore, the aim of this thesis was devoted to the development of computational methods to enable quantitative molecular imaging in PET, SPET and in vivo patient dosimetry with CMOS image sensors.

    The first task was to develop a novel quantitative dual isotope method for simultaneous assessments of regional lung ventilation and perfusion using a SPET technique. This method included correction routines for photon scattering, non uniform attenuation at two different photon energies (140 and 392 keV) and organ outline. This quantitative method was validated both with phantom experiments and physiological studies on healthy subjects.

    The second task was to develop and clinically apply a quantitative method for tumour to background activity uptake measurements using planar mammo-scintigraphy, with partial volume compensation.

    The third stage was to produce several computational models to assess the spatial resolution limitations in PET from the positron range, the annihilation photon non-collineairy and the photon depth of interaction.

    Finally, a quantitative image processing method for a CMOS image sensor for applications in ion beam therapy dosimetry was developed.

    From the obtained phantom and physiological results it was concluded that the methodologies developed for the simultaneous measurement of the lung ventilation and perfusion and for the quantification of the tumour malignancy grade in breast carcinoma were both accurate. Further, the obtained models for the influence that the positron range in various human tissues, and the photon emission non-collinearity and depth of interaction have on PET image spatial resolution, could be used both to optimise future PET camera designs and spatial resolution recovery algorithms. Finally, it was shown that the proton fluence rate in a proton therapy beam could be monitored and visualised by using a simple and inexpensive CMOS image sensor.

  • 324. Sang, R
    et al.
    Lutomiah, J
    Said, M
    Makio, A
    Koka, H
    Koskei, E
    Nyunja, A
    Owaka, S
    Matoke-Muhia, D
    Bukachi, S
    Lindahl, J
    Grace, D
    Bett, B
    Effects of Irrigation and Rainfall on the Population Dynamics of Rift Valley Fever and Other Arbovirus Mosquito Vectors in the Epidemic-Prone Tana River County, Kenya.2017In: Journal of medical entomology, ISSN 0022-2585, E-ISSN 1938-2928, Vol. 54, no 2, p. 460-470Article in journal (Refereed)
    Abstract [en]

    Rift Valley fever (RVF) is a mosquito-borne viral zoonosis that is found in most regions of sub-Saharan Africa, and it affects humans, livestock, and some wild ungulates. Outbreaks are precipitated by an abundance of mosquito vectors associated with heavy persistent rainfall with flooding. We determined the impact of flood-irrigation farming and the effect of environmental parameters on the ecology and densities of primary and secondary vectors of the RVF virus (RVFV) in an RVF-epidemic hotspot in the Tana River Basin, Kenya. Mosquito sampling was conducted in farms and villages (settlements) in an irrigated and a neighboring nonirrigated site (Murukani). Overall, a significantly higher number of mosquitoes were collected in farms in the irrigation scheme compared with villages in the same area (P < 0.001), or farms (P < 0.001), and villages (P = 0.03) in Murukani. In particular, key primary vectors of RVFV, Aedes mcintoshi Marks and Aedes ochraceous Theobald, were more prevalent in the farms compared with villages in the irrigation scheme (P = 0.001) both during the dry and the wet seasons. Similarly, there was a greater abundance of secondary vectors, particularly Culex univittatus Theobald and Culex pipiens (L.) in the irrigation scheme than in the Murukani area. Rainfall and humidity were positively correlated with mosquito densities, particularly the primary vectors. Adult floodwater mosquitoes and Mansonia spp. were collected indoors; immatures of Ae. mcintoshi and secondary vectors were collected in the irrigation drainage canals, whereas those of Ae. ochraceous and Aedes sudanensis Theobald were missing from these water bodies. In conclusion, irrigation in RVF endemic areas provides conducive resting and breeding conditions for vectors of RVFV and other endemic arboviruses.

  • 325.
    Schock, Helena
    Umeå University, Faculty of Medicine, Department of Medical Biosciences.
    Hormone concentrations during pregnancy and maternal risk of epithelial ovarian cancer2015Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Background: The aim of this thesis was to study the relationship of pre-diagnostic circulating concentrations of sex steroid hormones (androgens, estradiol, 17-hydroxyprogesterone, and progesterone), growth factors (insulin-like growth factor-I (IGF-I), placental growth hormone (GH)), sex hormone binding globulin (SHBG), and anti-Müllerian hormone (AMH) with risk of epithelial ovarian cancer (EOC) overall, and by tumor invasiveness and histology. A longitudinal study was used to assess patterns of hormonal changes during a single pregnancy, and in two consecutive pregnancies.

    Materials & Methods: A case-control study was nested within the Finnish Maternity Cohort and the Northern Sweden Maternity Cohort. A total of 1 052 EOC cases were identified through linkages with the cancer registries in both countries. For each case, 2-3 controls were selected. Cases and controls were matched on cohort, age and date at blood draw, as well as for parity at blood draw and at diagnosis (n=2 695). Odds ratios (OR) and corresponding 95% confidence intervals [CI] were estimated using conditional logistic regression. The longitudinal study was based on 71 pregnant Finnish women, who donated blood samples in each trimester of pregnancy.

    Results: Higher androgen concentrations were associated with an increased risk of overall EOC (e.g., testosterone ORT3 vs. T1: 1.56 [1.30-1.87], ptrend<0.0001), while the risk of endometrioid tumors increased with higher estradiol concentrations (ORT3 vs. T1: 2.76 [1.04-7.33], ptrend=0.03). Higher IGF-I was associated with a non-significant decrease in risk for invasive (ORT3 vs. T1: 0.79 [0.62-1.02], ptrend=0.07) and endometrioid tumors (ORT3 vs. T1: 0.55 [0.28-1.07], ptrend=0.07). The inverse association between IGF-I levels and risk of invasive EOC was stronger in analyses limited to women aged <55 years at diagnosis (ORT3 vs. T1: 0.74 [0.57-0.96], ptrend=0.03). No associations were observed between pre-diagnostic progesterone, SHBG, placental GH, and AMH with EOC risk overall, or by tumor invasiveness and histology.

    The longitudinal study showed that hormone concentrations were more strongly correlated between consecutive trimesters of a pregnancy than between the 1st and 3rd trimesters. Further, 3rd trimester hormone concentrations can be estimated from 1st or 2nd trimester measurements.

    Conclusion: Higher pre-diagnostic androgens, estradiol, and IGF-I are associated with EOC risk, and associations differ by tumor invasiveness and histology.

  • 326.
    Schock, Helena
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology. German Cancer Research Center, Heidelberg.
    Fortner, Renée T
    German Cancer Research Center, Heidelberg.
    Surcel, Heljä-Marja
    National Institute for Health and Welfare, Oulu, Finland.
    Grankvist, Kjell
    Umeå University, Faculty of Medicine, Department of Biobank Research. Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Pukkala, Eero
    School of Public Health, University of Tampere, Finland.
    Lehtinen, Matti
    School of Public Health, University of Tampere, Finland.
    Lundin, Eva
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Early pregnancy IGF-I and placental GH and risk of epithelial ovarian cancer: A nested case-control study2015In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 137, no 2, p. 439-447Article in journal (Refereed)
    Abstract [en]

    Insulin-like growth factor-I (IGF-I) signaling may promote ovarian tumor development by exerting mitotic, antiapoptotic and proangiogenic effects. During pregnancy, maternal production of IGF-I is regulated by placental growth hormone (GH). Parity is an established protective factor for ovarian cancer, however, no prior study has evaluated placental GH and IGF-I in pregnancy and epithelial ovarian cancer (EOC). Prior prospective studies on the association between IGF-I and EOC in nonpregnant populations were inconclusive and did not address associations in subtypes of EOC. Among members of the Finnish Maternity Cohort and the Northern Sweden Maternity Cohort, we identified 1,045 EOC cases, diagnosed after recruitment (1975-2008) and before March 2011 and 2,658 individually matched controls. Placental GH and IGF-I were measured in serum from the last pregnancy before EOC diagnosis or selection as control. We used conditional logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for tertiles and a doubling of hormone concentrations. Higher IGF-I was associated with a nonsignificant decrease in risk for invasive [ORT3 vs. T1 : 0.79 (0.62-1.02); ptrend  = 0.07] and endometrioid tumors [ORT3 vs. T1 : 0.55 (0.28-1.07); ptrend  = 0.07]. The protective association between higher IGF-I levels and risk of invasive EOC was stronger in analyses limited to women aged <55 years at diagnosis [ORT3 vs. T1 : 0.74 (0.57-0.96); ptrend  = 0.03]. Our study provides the first data on placental GH and IGF-I in pregnancy and EOC risk overall and by subtype. Our data suggest higher IGF-I levels in pregnancy may be associated with lower risk of invasive and endometrioid EOC.

  • 327.
    Schock, Helena
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology. Division of Cancer Epidemiology, German Cancer Research Center, Im Neuenheimer Feld 280, Heidelberg 69120, Germany.
    Surcel, Helja-Marja
    Oulu, Finland.
    Zeleniuch-Jacquotte, Anne
    Umeå University, Faculty of Medicine, Department of Biobank Research. New York, USA.
    Grankvist, Kjell
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Lakso, Hans-Åke
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Fortner, Renee Turzanski
    Heidelberg, Germany.
    Kaaks, Rudolf
    Heidelberg, Germany.
    Pukkala, Eero
    Helsinki, Finland; Tampere, Finland.
    Lehtinen, Matti
    Tampere, Finland.
    Toniolo, Paolo
    New York, USA; Lausanne, Switzerland.
    Lundin, Eva
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Early pregnancy sex steroids and maternal risk of epithelial ovarian cancer2014In: Endocrine-Related Cancer, ISSN 1351-0088, E-ISSN 1479-6821, Vol. 21, no 6, p. 831-844Article in journal (Refereed)
    Abstract [en]

    Well-established associations between reproductive characteristics and epithelial ovarian cancer (EOC) support an involvement of sex steroid hormones in the etiology of EOC. Limited previous studies have evaluated circulating androgens and the risk of EOC, and estrogens and progesterone have been investigated in only one of the previous studies. Furthermore, there is little data on potential heterogeneity in the association between circulating hormones and EOC by histological subgroup. Therefore, we conducted a nested case-control study within the Finnish Maternity Cohort and the Northern Sweden Maternity Cohort to investigate the associations between circulating pre-diagnostic sex steroid concentrations and the histological subtypes of EOC. We identified 1052 EOC cases among cohort members diagnosed after recruitment (1975-2008) and before March 2011. Up to three controls were individually matched to each case (n=2694). Testosterone, androstenedione, 17-hydroxyprogesterone (17-OHP), progesterone, estradiol (E-2), and sex hormone-binding globulin levels were measured in serum samples collected during the last pregnancy before EOC diagnosis. We used conditional logistic regression to estimate odds ratios (ORs) and 95% CIs. Associations between hormones and EOC differed with respect to tumor histology and invasiveness. Sex steroid concentrations were not associated with invasive serous tumors; however, doubling of testosterone and 17-OHP concentration was associated with approximately 40% increased risk of borderline serous tumors. A doubling of androgen concentrations was associated with a 50% increased risk of mucinous tumors. The risk of endometrioid tumors increased with higher E-2 concentrations (OR: 1.89 (1.20-2.98)). This large prospective study in pregnant women supports a role of sex steroid hormones in the etiology of EOC arising in the ovaries.

  • 328.
    Schock, Helena
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences. German Cancer Research Center, Heidelberg, Germany.
    Zeleniuch-Jacquotte, A
    New York University school of medicine, New York, USA.
    Lundin, Eva
    Umeå University, Faculty of Medicine, Department of Medical Biosciences.
    Grankvist, Kjell
    Umeå University, Faculty of Medicine, Department of Medical Biosciences.
    Lakso, Hans-Åke
    Umeå University, Faculty of Medicine, Department of Medical Biosciences.
    Idahl, Annika
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    Surcel, HM
    National Institute for Health and Welfare, Oulu, Finland.
    Fortner, RT
    German Cancer Research Center, Heidelberg, Germany.
    Longitudinal Assessment of Pregnancy HormonesManuscript (preprint) (Other academic)
    Abstract [en]

    Evidence suggests that the hormonal milieu of pregnancy is an important determinant of subsequent cancer and other chronic diseases in both the mother and the offspring. How well a single blood specimen collected during a pregnancy characterizes exposure to these hormones throughout gestation, and also in subsequent pregnancies, is not well understood. We used serial serum samples from 71 pregnant women (25 primiparous, 25 biparous, and 21 with 2 consecutive pregnancies) with natural, complication-free pregnancies and a healthy offspring at term who participated in a population-based screening trial for congenital infections in Finland between January 1st, 1988 and June 30, 1989 and provided a blood sample in each trimester. Hormone levels were more strongly correlated between consecutive trimesters of a pregnancy than between the 1st and 3rd trimester (e.g. estradiol, 1st vs. 2nd and 2nd vs. 3rd trimester r=0.51 and r=0.60, p<0.01; 1st vs. 3rd trimester r=0.32, p<0.05). Concentrations of sRANKL remained stable throughout gestation, whereas estradiol, estrone, progesterone, testosterone, prolactin, and osteoprotegerin increased throughout pregnancy. First trimester hormone concentrations explained less of the variation in the third trimester on their own than second trimester hormone levels (e.g. estradiol R²T1=16% and R²T2=42%). Addition of maternal (e.g., smoking) and/or child characteristics (e.g., sex) improved the accuracy of the 3rd trimester estimates for some of the hormones. In conclusion, one hormone measurement in early pregnancy, in conjunction with maternal and fetal characteristics, permits estimation of 3rd trimester hormone concentrations.

  • 329.
    Schöld, Caroline
    Halmstad University, School of Business and Engineering (SET).
    Framtagning av rutiner för enhetlig och  effektiv handläggning: – Förvildade och/eller hemlösa katter i Skåne län2010Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    The responsibility for handling matters concerning animal protection in Sweden moved from

    the municipalities to the county administration in January 2009. This reorganization meant that

    many inspectors, whom previously had worked on their own, now found themselves working

    in teams with new colleagues. This situation increased the needs for co-ordinated routines

    describing the handling of cases in order to make the new teamwork run more smoothly.

     

    The purpose of this study was to create a document containing handling routines for cases

    concerning feral and/or homeless cats and to generalize the result to create general advise

    concerning the work process The challenge when developing a useful routine document is to

    capture the most important details without losing a comprehensive view. This report starts with

    a general description of the process for developing a routine document, followed by a

    description of how a routine document for handeling feral and/or homeless cats was developed

    for the county administration in the Skåne region. The finished routine document focuses on

    the importance of gathering information when the cat case is reported in to the county

    administration, prioritization of cases, documentation of control work and preventive work

    methods.

  • 330. Seele, Jana
    et al.
    Beineke, Andreas
    Hillermann, Lena-Maria
    Jaschok-Kentner, Beate
    von Pawel-Rammingen, Ulrich
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).
    Valentin-Weigand, Peter
    Baums, Christoph Georg
    The immunoglobulin M-degrading enzyme of Streptococcus suis, Ide(Ssuis), is involved in complement evasion2015In: Veterinary research (Print), ISSN 0928-4249, E-ISSN 1297-9716, Vol. 46, article id 45Article in journal (Refereed)
    Abstract [en]

    Streptococcus (S.) suis is one of the most important pathogens in pigs causing meningitis, arthritis, endocarditis and serositis. Furthermore, it is also an emerging zoonotic agent. In our previous work we identified a highly specific IgM protease in S. suis, designated IdeSsuis. The objective of this study was to characterize the function of IdeSsuis in the host-pathogen interaction. Edman-sequencing revealed that Ide(Ssuis) cleaves the heavy chain of the IgM molecule between constant domain 2 and 3. As the C1q binding motif is located in the C3 domain, we hypothesized that IdeSsuis is involved in complement evasion. Complement-mediated hemolysis induced by porcine hyperimmune sera containing erythrocyte-specific IgM was abrogated by treatment of these sera with recombinant IdeSsuis. Furthermore, expression of IdeSsuis reduced IgM-triggered complement deposition on the bacterial surface. An infection experiment of prime-vaccinated growing piglets suggested attenuation in the virulence of the mutant 10 Delta IdeSsuis. Bactericidal assays confirmed a positive effect of IdeSsuis expression on bacterial survival in porcine blood in the presence of high titers of specific IgM. In conclusion, this study demonstrates that IdeSsuis is a novel complement evasion factor, which is important for bacterial survival in porcine blood during the early adaptive (IgM-dominated) immune response.

  • 331. Seele, Jana
    et al.
    Hillermann, Lena-Maria
    Beineke, Andreas
    Seitz, Maren
    von Pawel-Rammingen, Ulrich
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine). Umeå University, Faculty of Medicine, Umeå Centre for Microbial Research (UCMR).
    Valentin-Weigand, Peter
    Baums, Christoph G.
    The immunoglobulin M-degrading enzyme of Streptococcus suis, Ide(Ssuis), is a highly protective antigen against serotype 22015In: Vaccine, ISSN 0264-410X, E-ISSN 1873-2518, Vol. 33, no 19, p. 2207-2212Article in journal (Refereed)
    Abstract [en]

    Streptococcus suis (S. suis) is a major porcine pathogen causing meningitis, arthritis and several other pathologies. Recently, we identified a highly specific immunoglobulin M degrading enzyme of S. suis, designated IdeSsuis, which is expressed by various serotypes. The objective of this work was to access the immunogenicity and protective efficacy of a recombinant vaccine including IdeSsuis. Vaccination with rIdeSsuis elicited antibodies efficiently neutralizing the IgM protease activity. Importantly, 18 piglets vaccinated with rIdeSsuis alone or in combination with bacterin priming were completely protected against mortality and severe morbidity after S. suis serotype 2 challenge. In contrast, 12 of the 17 piglets either treated with the placebo or primed with the bacterin only, succumbed to S. suis disease. Immunity against Idessuis was associated with increased killing of S. suis wt in porcine blood ex vivo leading to a tenfold difference in the bacterial survival factor in blood of placebo-treated and rIdeSsuis-vaccinated piglets. In conclusion, the results of this study indicate that rIdeSsuis is a highly protective antigen in pigs.

  • 332.
    Segerdahl, M.
    et al.
    Karolinska Inst, Unit Anesthesia, Dept Clin Sci Intervent & Technol, Stockholm, Sweden.
    Warrén-Stomberg, Margareta
    University of Skövde, School of Life Sciences.
    Rawal, N.
    Örebro Univ Hosp, Dept Anesthesia & Intens Care, Örebro, Sweden .
    Brattwall, M.
    Sahlgrenska Univ Hosp Molndal, Unit Day Care Surg, Gothenburg, Sweden.
    Jakobsson, J.
    Karolinska Inst, Unit Anesthesia, Dept Physiol & Pharmacol, Stockholm, Sweden.
    Clinical practice and routines for day surgery in Sweden2008In: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 52, no 1, p. 117-124Article in journal (Refereed)
    Abstract [en]

    Background: Day surgery is common in paediatric surgical practice. Safe routines including parental and child information in order to optimise care and reduce anxiety are important. Most day surgery units are not specialised in paediatric care, which is why specific paediatric expertise is often lacking.

    Methods: We studied the practice of paediatric day surgery in Sweden by a questionnaire survey sent to all hospitals, obtaining an 88% response rate. Three specific paediatric cases were enquired for in more detail.

    Results: The proportion of paediatric day surgery vs. in-hospital procedures was 46%. Seventy-one out of 88 responding units performed paediatric day surgery. All units had anxiolytic pre-medication as a routine in 1–6-year-olds, and in 7–16-year-olds at 60% of the units. Most units performed circumcision and adenoidectomy, while 33% performed tonsillectomy. Anaesthesia induction was intravenous in older children, and also in 1–6-year-olds at 50% of the units. Parental presence at induction was mandatory. Post-operatively, 93% of units routinely assessed pain. Paracetamol and NSAIDs were the most common analgesics, as monotherapy or combined with rescue medication in the recovery as IV morphine. At 42% of units, take-home bags of analgesics were provided, covering 1–3 days of treatment. Pain was the most frequent complaint on follow-up. Micturition difficulties were common after circumcision, nausea after adenoidectomy and nutrition difficulties after tonsillectomy.

    Conclusions: In Sweden, most day surgery units perform paediatric surgery, most children receive pre-medication, anaesthesia is induced IV and take-home analgesics paracetamol and or NSAIDs are often provided. Still, pain is a common complaint after discharge.

  • 333.
    Selden, A. I.
    et al.
    Department of Occupational and Environmental Medicine, Örebro University Hospital, Örebro, Sweden.
    Calo, A.
    Study Consultancy Inc., Örebro, Sweden.
    Molleby, G.
    Department of Occupational and Environmental Medicine, Örebro University Hospital, Örebro, Sweden.
    Hultgren, Olof
    Örebro University, School of Medicine, Örebro University, Sweden. Department of Clinical Microbiology, Örebro University Hospital, Region Örebro County, Örebro, Sweden.
    Chironomid midge sensitization in sewage workers: case study2013In: Medical and Veterinary Entomology, ISSN 0269-283X, E-ISSN 1365-2915, Vol. 27, no 3, p. 346-348Article in journal (Refereed)
    Abstract [en]

    Non-biting chironomid midges (Diptera: Chironomidae) may cause sensitization and allergic reactions in humans and have recently been identified as a potential health problem in Swedish municipal sewage treatment plants. To investigate, on a pilot scale, the allergenic potential of chironomids in sewage workers, all workers (n = 8) at a sewage treatment plant and local controls (n = 16) completed a symptom questionnaire, underwent measurement of the fraction of nitric oxide in exhaled air, spirometry, and provided serum samples for the determination of atopy status and the prevalence of specific immunoglobulin E (IgE) antibodies against Chironomus thummi (Chi t) using a commercial fluorescence enzyme immunoassay (FEIA). Three sewage workers (38%) but no controls (0%) were FEIA positive for C. thummi-specific IgE antibodies (P < 0.05). No other health-related findings were significantly different between the groups. The study suggested that occupational exposure to Chironomids may cause sensitization with circulating IgE-antibodies in sewage workers.

  • 334.
    Sellman, Stefan
    Linköping University, Department of Physics, Chemistry and Biology, Theoretical Biology. Linköping University, Faculty of Science & Engineering.
    Quantifying Risk in Epidemiological and Ecological Contexts2018Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The rates of globalization and growth of the human population puts ever increasing pressure on the agricultural sector to intensify and grow more complex, and with this intensification comes an increased risk of outbreaks of infectious livestock diseases. At the same time, and for the same reasons, the detrimental effect that humans have on other species with which we share the environment has never been more apparent, as the current rates of species loss from ecological communities rival those of ancient mass extinction events. In order to find ways to lessen the effects of and eventually solve such problems we need ways to quantify the risks involved, something that can be difficult when for instance the sheer size or sensitivity of the systems makes practical experimentation unsuitable. For these situations mathematical models have become invaluable tools due to their flexibility and noninvasiveness. This thesis presents four works involving the quantification of risk in livestock epidemic and ecological contexts using mathematical models. Two of them deal with extinctions of species within model ecological communities, and how species interactions play a role in the identity of the lost species following perturbations to specific species (Papers I and II). The other two regard how the spatial layout of the underlying population of livestock premises affect the risk of foot and mouth disease outbreaks among farms in the USA, and how models of such outbreaks can be optimized to improve their usefulness (Papers III and IV).

    Ecological communities consist of species and the often intricate pattern of interactions between them. These interspecies connections can propagate effects caused by disturbances in one end of the network, through the community via the links, to other parts of the network. In some cases, a reduction in the abundance of one species can cause the extinction of a second species before the first species disappears, something called functional extinction. Despite this, many conservation efforts revolve around simply keeping populations of single species at a high enough level for their own survival. In a model setting, the study of Paper I explores and attempts to quantify how common such functional extinctions are in relation to the alternative outcome that a perturbed species itself becomes extinct. This is done by first constructing stable model food webs describing predator-prey interactions of up to 50 species, parameterized through allometric relationships between metabolic processes and body size. Then the smallest amount of extra mortality that can be applied to each and every species in the web before any species become extinct is determined. The study shows that in these model communities, more often than not (>80%) another species, rather than the species that is subjected to the additional mortality will be the one to become extinct first.

    The approach of Paper I is taken further in Paper II by applying the same methodology to ecological networks that include mixtures of both antagonistic (predator-prey) and mutualistic (e.g. pollination and seed dispersal) interactions. The results further reinforce the findings of Paper I, and show that ecological networks containing a mixture of antagonistic and mutualistic interactions are more sensitive to functional extinctions than purely antagonistic or purely mutualistic ones, an important finding considering the diversity of interaction types in natural systems. Furthermore, the type of species found to have the lowest threshold before becoming functionally extinct were those with a mixture of interaction types, such as pollinating insects. Both Paper I and II consolidate the notion that when doing conservation work it is important to have the entire community in mind by considering the population sizes that are viable from a multi-species perspective, rather than just focusing on the minimum population sizes that are viable for the individual species.

    In Papers III and IV the focus changes somewhat, from models of ecological systems to models of how infectious livestock disease spread between farms in spatially explicit contexts. For this kind of model, information about the spatial distribution of the hosts is of course crucial, but not always readily available. In the USA, the only available information about livestock premises demography is aggregated at the county scale, meaning that the spatial distribution of the premises within each county is unknown. However, a method exists to simulate realistic stochastic spatial configurations of premises using a set of predictor variables, such as topology, climate and roads. An alternative approach that have been used previously is to assume a uniformly random spatial distribution of premises within each county. But to what extent does the choice between these two methods affect the model’s evaluation of the risk of disease outbreaks? In Paper III, this is analyzed specifically for foot and mouth disease. Through simulated outbreaks and by looking at the reproductive ratio of the disease, the outbreak dynamics within the two different spatial configurations of premises are compared. The results show that there is a clear difference in the risk of outbreaks between them, with the non-uniform distributions showing a general pattern of higher outbreak risk. However this difference is dependent on the size and geographic location of the county that the outbreak start in with larger counties in the west of the US showing a stronger effect.

    When running numerical simulations with large scale models such as the one used in Paper III, a considerable amount of replication is usually necessary in order to account for the high degree of stochasticity inherent to the problem. Even further replication is required when performing sensitivity analyses of model parameters or when exploring different scenarios, for instance when trying to determine the optimal control strategy for a disease. For this reason, the amount and quality of results that can be produced by such studies can quickly become limited by the availability of computational resources. Finding ways to optimize the computations involved with regard to simulation time is therefore of great value as it can be directly related to the robustness of the results. In Paper IV, an efficient optimization method for the kind of kernel-based local disease spread model used in paper III is presented. The method revolves around constructing a grid structure that is overlaid on top of the farm landscape and dividing the infection process into two steps, first evaluating if any farms within one of the grid squares can become infected given an over-estimation of the probability of infection, and then only if so, evaluate actual infection of a subset of the farms within the receiving square. The method is compared to similar published methods and is shown to be more efficient in most cases, while also being easy to implement and understand. Furthermore, while other methods often involve approximations of the transmission process in order to improve computational speed, the method of Paper IV is shown to be exact. This is a major advantage, since with an approximative method the extent to which the results are affected by the simplification is unknown unless the effect of the approximation is explicitly quantified. In most cases, such quantification would require extensive simulations with the unsimplified approach, something which of course may not be feasible.

  • 335.
    Sepa, Anneli
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    The Stress Hypothesis: Implications for the induction of diabetes-related autoimmunity in children?2004Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Background: Second to Finland, Sweden has the world’s highest incidence of type 1 diabetes. Experiences of serious life events have retrospectively been shown to constitute a risk factor for the development of this disease, probably via the biological stress response. Parenting stress and maternal attachment insecurity are other important sources of stress in early childhood.

    Psychological stress increases the need for insulin and may induce insulin resistance, which might add extra pressure on the insulin-producing beta cells in the pancreas (beta-cell stress).

    The aim of the current thesis was to propose and start investigating a stress hypothesis – namely that psychological stress may induce insulin resistance leading to beta-cell stress, which could trigger an autoimmune reaction towards beta-cells in genetically predisposed children. When all the beta cells have been destroyed, insulin can no longer be produced in the body and type 1 diabetes becomes manifest.

    Methods: Families from the prospective population-based ABIS-project, which follows approximately 17 000 children, participated in the empirical studies of the current thesis. The mothers completed questionnaires, including various measures of psychological stress (e.g. parenting stress and experiences of serious life events) and socio-demographic background, at the birth of the child and when the child was 1 as well as 2.5 years of age. Maternal attachment insecurity was assessed with the Adult Attachment Interview. Blood samples drawn from the children at 1 and 2.5 years of age were analyzed for type 1 diabetes-related autoantibodies towards Tyrosine phosphatase (IA-2) and Glutamic Acid Decarboxylase (GAD).

    Findings and Conclusions: Parenting stress and experiences of serious life events like divorce and maternal exposure to violence were associated with the induction of diabetes-related autoimmunity in early childhood, possibly via insulin resistance and beta-cell stress. The risk of developing diabetesrelated autoimmunity after parental divorce or mothers’ exposure to violence was about threefold. None of the results were explained by any of the potential confounding factors analyzed. These results support and strengthen the stress hypothesis, which warrants further investigation.

    Mothers’ attachment insecurity was not associated with the induction of diabetes-related autoimmunity in their infants. However, this lack of association was perhaps due to methodological constraints.

    The vast majority of the parents were calmed or unaffected concerning their participation in the ABIS-project, suggesting that large-scale medical screening-projects in the general population are not in themselves a cause for worry and can be performed without causing increased anxiety.

  • 336.
    Shariatgorji, Mohammadreza
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Nilsson, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Goodwin, Richard J A
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Källback, Patrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Schintu, Nicoletta
    Zhang, Xiaoqun
    Crossman, Alan R
    Bezard, Erwan
    Svenningsson, Per
    Andrén, Per E
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Direct targeted quantitative molecular imaging of neurotransmitters in brain tissue sections2014In: Neuron, ISSN 0896-6273, E-ISSN 1097-4199, Vol. 84, no 4, p. 697-707Article in journal (Refereed)
    Abstract [en]

    Current neuroimaging techniques have very limited abilities to directly identify and quantify neurotransmitters from brain sections. We have developed a molecular-specific approach for the simultaneous imaging and quantitation of multiple neurotransmitters, precursors, and metabolites, such as tyrosine, tryptamine, tyramine, phenethylamine, dopamine, 3-methoxytyramine, serotonin, GABA, glutamate, acetylcholine, and L-alpha-glycerylphosphorylcholine, in histological tissue sections at high spatial resolutions. The method is employed to directly measure changes in the absolute and relative levels ofneurotransmitters in specific brain structures in animal disease models and in response to drug treatments, demonstrating the power of mass spectrometry imaging in neuroscience.

  • 337. Shome, Rajeswari
    et al.
    Deka, Ram Pratim
    Milesh, Ligi
    Sahay, Swati
    Grace, Delia
    Lindahl, Johanna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Coxiella seroprevalence and risk factors in large ruminants in Bihar and Assam, India.2019In: Acta Tropica, ISSN 0001-706X, E-ISSN 1873-6254, Vol. 194, p. 41-46Article in journal (Refereed)
    Abstract [en]

    Coxiellosis is a zoonotic disease caused by the ubiquitous bacteria Coxiella burnetii, which can be spread either through ticks or through body fluids. In humans the infection is characterized by a febrile disease; ruminants may abort and reduce their milk yield, causing serious production losses for the farmer. In India, the disease has been known to be present since the 1970s, but little is known about the epidemiology in most states. In this cross-sectional survey in the two states of Assam and Bihar, 520 households were interviewed for risk factors, and serum samples from 744 dairy animals were analyzed using ELISA as well as PCR. Out of the farms, 17.4% had at least one seropositive animal, with significantly higher seroprevalence in Bihar (27.1%) than Assam (5.8%); and significantly more sero-positive farms in urban areas (23.1%) than rural (12.2%). On an individual animal level, 14.1% were seropositive, with higher prevalence among buffaloes than cows (28.0% versus 13.6%). Out of the seropositive animals, 10.6% had aborted during the last three years, and 37.5% had experienced problems with repeat breeding: both higher than in non-seropositive animals. In conclusion, this study indicates that coxiellosis is potentially an important cause of reproductive failures and production losses in dairy animals. The high prevalence, especially in urban areas, is a public health risk. Further research is needed to elucidate the epidemiology and identify mitigation options that could work in the different settings of different Indian states.

  • 338. Shome, Rajeswari
    et al.
    Deka, Ram Pratim
    Sahay, Swati
    Grace, Delia
    Lindahl, Johanna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Seroprevalence of hemorrhagic septicemia in dairy cows in Assam, India.2019In: Infection Ecology & Epidemiology, ISSN 2000-8686, E-ISSN 2000-8686, Vol. 9, no 1, article id 1604064Article in journal (Refereed)
    Abstract [en]

    Hemorrhagic septicemia (HS) is a highly fatal disease caused by Pasteurella multocida that often cause outbreaks in buffalo and cattle in India, and thus is a major cause of production losses. It is one of the livestock diseases with the highest mortality, and despite available vaccines, outbreaks still occur. To assess the seroprevalence in the state of Assam, Northeast India, 346 serum samples from cows from 224 randomly selected households, from both urban and rural areas of three districts, were tested with a commercial ELISA. In total 88 cows were seropositive (25.4%), and indigenous cattle were significantly more seropositive (33.5%) compared to the crossbred cattle (18.5%) (p = 0.002). Herd prevalence was 35.7%, and more rural farms (47.4%) were positive compared to the urban farms (23.6%) (p < 0.001). No other risk factors were identified in this study. Only one farm had vaccinated against HS, but there were no seropositive animals detected in that herd. This study shows that HS is highly prevalent in Assam. Considering the importance of dairy production in India, and the dependence of the rural Assam population on farming and livestock keeping, more extensive vaccination campaigns would be important.

  • 339.
    Singh Parihar, Vishal
    Swedish University of Agricultural Sciences, Uppsala, Sweden.
    Zoonotic Aspects of Listeria monocytogenes: with Special Reference to Bacteriology2004Independent thesis Advanced level (degree of Master (Two Years)), 80 credits / 120 HE creditsStudent thesis
    Abstract [en]

    Listeria monocytogenes is a non acid-fast, Gram-positive facultative anaerobic pathogen, which is considered as food- and feed-borne. Whereas poor quality silage is the main cause of animal listeriosis, contaminated food of animal origin is the main cause of human listeriosis. That the raw material for food is of animal origin does not necessarily mean that the L. monocytogenes bacteria also spring from animals. The bacteria may have contaminated the food product while processed. Knowledge of the direct or indirect transmission of L. monocytogenes between animals and humans, via e.g. foods, is limited. To highlight the zoonotic aspects of L. monocytogenes we need more comparative data concerning isolates of animal and human origin. The aim of the present study was to characterize clinical L. monocytogenes isolates from different animal’s species and to compare the patterns with those obtained from previously characterized clinical human strains. Animal isolates were characterized by use of restriction enzymes Asc I and Apa I followed by PFGE. Out of 104 animal strains 47 belonged to clonal types identical or closely related to clonal types seen among clinical human strains. The clonal types shared by animals and humans may indicate that there is an exchange of L. monocytogenes strains between these two groups or there may be a common environmental pool of strains. On the other hand, 42 animal strains belonged to clonal types that were unfamiliar to our collection of human strains. Finally, 15 animal isolates distributed into eight clonal types  yielded Asc I profiles familiar to our human clonal types yet unfamiliar Apa I profiles. Human and animal isolates of L. monocytogenes have rarely been compared by use of PFGE. Further studies is needed to highlight routes of transmissions between animals and humans, e.g., via food.

  • 340.
    Sjøvold, Torstein
    et al.
    Stockholm University, Faculty of Humanities, Osteology Unit.
    Hufthammer, Anne Karin
    Costal cartilage fractures among artiodactyles and perissodactyles2008In: Veterinarija ir Zootechnika, Vol. 43(65), p. 84-89Article in journal (Refereed)
    Abstract [en]

    In artiodactyles and perissodactyles the interior of the costal cartilages ossify, forming a spongy, osseous tissue. Recently, it has been discovered that such ossifications frequently display visible lines perpendicular to the cur-vature of the ossification. Such lines are not rare, and often several lines along the same costal cartilage are observed. Macerated ossified costal cartilages frequently, but not always, split into short, bony stabs with straight, cutoff ends, sometimes retaining organic matter encircled within a bony periphery. In archaeological materials such bony stabs areoccasionally observed, and are just denoted “costal cartilages” if recognized. The cause of these structures is not clear. Some may be regarded as transverse splits of the ossifications along a weakness zone, but in other cases the cause isobviously a fracture with more or less extensive callus formation. The smooth surfaces are typical and cannot be con-fused with a secondary fracture, which occur after deposition or maceration. The smooth ends of a healed fracture al-ways display a thin layer of compact tissue, while a secondary fracture is irregular and displays the spongy tissue. Thus, they may be considered as healed micro or macro fractures, where fusion of the fractured ends had occurred along theperiphery of the ossification. In other cases, however, healing may involve dislocation prior to the healing process, ex-tensive callus formation, lipping or formation of pseudoarthroses. How such an injury affected the animal is not gener-ally known. However, in the cases of dislocation and extensive bony reaction to the fracture, it is highly probable that the wellbeing of the animal was influenced by the injury.

  • 341.
    Skoglund, Björn
    Linköping University, Department of Clinical and Experimental Medicine, Orthopaedics and Sports Medicine . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Orthopaedic Centre, Department of Orthopaedics Linköping.
    Following the mevalonate pathway to bone heal alley2007Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The mevalonate pathway is an important biosynthetic pathway, found in all cells of virtually all known pro- as well as eukaryotic organisms. This thesis is an investigation into the use of two drugs, originally developed for different applications, but both affecting the mevalonate pathway, in to models of fracture repair.

    Using two different rodent models of fracture repair, a commonly used cholesterol lowering drug (statin) and two drugs used to treat osteoporosis (bisphosphonate) were applied both systemically as well as locally in order to enhance fracture repair.

    Papers I and II investigate the potential of simvastatin to improve the healing of femoral fractures in mice. Papers III and IV explore the use of two bisphosphonates to improve early fixation of stainless steel screws into rat bone.

    The statin simvastatin lead to an increased strength of the healing cellus. The application of bisphosphonates increased early screw fixation.

    It seems clear that both drugs have uses in orthopaedic applications. One interesting avenue of further research would be to combine the two classes of drugs and see if we can get the benefits while at the same time diminishing the drawbacks.

  • 342.
    Slinde, Frode
    University of Skövde, School of Life Sciences.
    Vad behöver du för information för att göra ett bra arbete som dietist2007In: Dietistaktuellt, ISSN 1102-9285, Vol. 18, no 5, p. 28-28Article in journal (Other (popular science, discussion, etc.))
  • 343.
    Spoerry, Christian
    et al.
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine). Umeå University, Faculty of Medicine, Umeå Centre for Microbial Research (UCMR).
    Seele, Jana
    Valentin-Weigand, Peter
    Baums, Christoph G.
    von Pawel-Rammingen, Ulrich
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine). Umeå University, Faculty of Medicine, Umeå Centre for Microbial Research (UCMR).
    Identification and Characterization of IgdE, a Novel IgG-degrading Protease of Streptococcus suis with Unique Specificity for Porcine IgG.2016In: Journal of Biological Chemistry, ISSN 0021-9258, E-ISSN 1083-351X, Vol. 291, no 15, p. 7915-7925Article in journal (Refereed)
    Abstract [en]

    Streptococcus suis is a major endemic pathogen of pigs causing meningitis, arthritis, and other diseases. Zoonotic S. suis infections are emerging in humans causing similar pathologies as well as severe conditions such as toxic shock-like syndrome. Recently, we discovered an IdeS family protease of S. suis that exclusively cleaves porcine IgM and represents the first virulence factor described, linking S. suis to pigs as their natural host. Here we report the identification and characterization of a novel, unrelated protease of S. suis that exclusively targets porcine IgG. This enzyme, designated IgdE for immunoglobulin G-degrading enzyme of S. suis, is a cysteine protease distinct from previous characterized streptococcal immunoglobulin degrading proteases of the IdeS family and mediates efficient cleavage of the hinge region of porcine IgG with a high degree of specificity. The findings that all S. suis strains investigated possess the IgG proteolytic activity and that piglet serum samples contain specific antibodies against IgdE strongly indicate that the protease is expressed in vivo during infection and represents a novel and putative important bacterial virulence/colonization determinant, and a thus potential therapeutic target.

  • 344. Spörndly-Nees, Ellinor
    et al.
    Ekstedt, Elisabeth
    Magnusson, Ulf
    Fakhrzadeh, Azadeh
    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.
    Luengo Hendriks, Cris L.
    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.
    Holm, Lena
    Effect of pre-fixation delay and freezing on mink testicular endpoints for environmental research2015In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 10, no 5, article id e0125139Article in journal (Refereed)
  • 345.
    Srithunyarat, T.
    et al.
    Swedish Univ Agr Sci, Dept Clin Sci, Box 7054, SE-75007 Uppsala, Sweden;Khon Kaen Univ, Dept Surg & Theriogenol, Fac Vet Med, Khon Kaen 40002, Thailand.
    Hagman, R.
    Swedish Univ Agr Sci, Dept Clin Sci, Box 7054, SE-75007 Uppsala, Sweden.
    Hoglund, O. V.
    Swedish Univ Agr Sci, Dept Clin Sci, Box 7054, SE-75007 Uppsala, Sweden.
    Stridsberg, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemical endocrinology.
    Hanson, J.
    Swedish Univ Agr Sci, Dept Clin Sci, Box 7054, SE-75007 Uppsala, Sweden.
    Lagerstedt, A. S.
    Swedish Univ Agr Sci, Dept Clin Sci, Box 7054, SE-75007 Uppsala, Sweden.
    Pettersson, A.
    Swedish Univ Agr Sci, Dept Clin Sci, Box 7054, SE-75007 Uppsala, Sweden.
    Catestatin, vasostatin, cortisol, and visual analog scale scoring for stress assessment in healthy dogs2018In: Research in Veterinary Science, ISSN 0034-5288, E-ISSN 1532-2661, Vol. 117, p. 74-80Article in journal (Refereed)
    Abstract [en]

    The neuroendocrine glycoprotein chromogranin A is a useful biomarker for stress in humans. Chromogranin A epitopes catestatin and vasostatin can be measured in dogs using radioimmunoassays. The objective of this study was to evaluate catestatin and vasostatin as canine stress biomarkers in a clinical setting. Blood and saliva were collected from 33 healthy dogs that were familiar with sampling procedures and the animal hospital environment (control group) and 30 healthy dogs that were unacquainted (stress group). During sampling, stress behavior was scored by the same observer using visual analog scale (VAS). Plasma was analyzed for catestatin and vasostatin, serum for cortisol, and saliva for catestatin. Differences between groups were analyzed using two sample t-tests and P < 0.05 was considered significant. Stress behavior VAS score in the control group was significantly lower than in the stress group during blood (P = 0.002) and saliva (P = 0.0009) sampling. Serum cortisol and saliva catestatin concentrations in the stress group were higher than the control group (P = 0.003 and P < 0.0001, respectively). Serum cortisol concentrations were correlated with those of saliva (r = 0.34, P = 0.04) and plasma catestatin (r = 0.29, P = 0.03). Plasma catestatin and vasostatin did not differ significantly between groups. In conclusion, concentrations of saliva catestatin, and serum cortisol, and stress behavior VAS scores were significantly higher in the stress group. The results indicate that saliva catestatin may be useful as a biomarker for acute psychological stress in dogs.

  • 346.
    Srithunyarat, Thanikul
    et al.
    Swedish Univ Agr Sci, Dept Clin Sci, Box 7504, S-75007 Uppsala, Sweden.;Khon Kaen Univ, Fac Vet Med, Dept Surg & Theriogenol, Khon Kaen 40002, Thailand..
    Hagman, Ragnvi
    Swedish Univ Agr Sci, Dept Clin Sci, Box 7504, S-75007 Uppsala, Sweden..
    Höglund, Odd V.
    Swedish Univ Agr Sci, Dept Clin Sci, Box 7504, S-75007 Uppsala, Sweden..
    Olsson, Ulf
    Swedish Univ Agr Sci, Unit Appl Stat & Math, Box 7032, S-75007 Uppsala, Sweden..
    Stridsberg, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemical endocrinology. Uppsala Univ, Dept Med Sci, S-75185 Uppsala, Sweden..
    Jitpean, Supranee
    Khon Kaen Univ, Fac Vet Med, Dept Surg & Theriogenol, Khon Kaen 40002, Thailand..
    Lagerstedt, Anne-Sofie
    Swedish Univ Agr Sci, Dept Clin Sci, Box 7504, S-75007 Uppsala, Sweden..
    Pettersson, Ann
    Swedish Univ Agr Sci, Dept Clin Sci, Box 7504, S-75007 Uppsala, Sweden..
    Catestatin and vasostatin concentrations in healthy dogs2017In: ACTA VETERINARIA SCANDINAVICA, ISSN 0044-605X, Vol. 59, article id 1Article in journal (Refereed)
    Abstract [en]

    Background: The neuroendocrine glycoprotein chromogranin A is a useful biomarker in humans for neuroendocrine tumors and stress. Chromogranin A can be measured in both blood and saliva. The objective of this study was to investigate concentrations of and correlation between the chromogranin A epitopes catestatin and vasostatin in healthy dogs accustomed to the sample collection procedures. Blood and saliva samples were collected from 10 research Beagle dogs twice daily for 5 consecutive days, and from 33 privately-owned blood donor dogs in association with 50 different blood donation occasions. All dogs were familiar with sample collection procedures. During each sampling, stress behavior was scored by the same observer using a visual analog scale (VAS) and serum cortisol concentrations. Catestatin and vasostatin were analyzed using radioimmunoassays for dogs. Results: The dogs showed minimal stress behavior during both saliva sampling and blood sampling as monitored by VAS scores and serum cortisol concentrations. Few and insufficient saliva volumes were obtained and therefore only catestatin could be analyzed. Catestatin concentrations differed significantly and did not correlate significantly with vasostatin concentrations (P < 0.0001). Age, gender, breed, and time of sample collection did not significantly affect concentrations of plasma catestatin, vasostatin, and saliva catestatin. Conclusions: The normal ranges of plasma catestatin (0.53-0.98 nmol/l), vasostatin (0.11-1.30 nmol/l), and saliva catestatin (0.31-1.03 nmol/l) concentrations in healthy dogs accustomed to the sampling procedures were determined. Separate interpretation of the different chromogranin A epitopes from either saliva or plasma is recommended.

  • 347. Srithunyarat, Thanikul
    et al.
    Hagman, Ragnvi
    Höglund, Odd V
    Stridsberg, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemical endocrinology.
    Olsson, Ulf
    Hanson, Jeanette
    Nonthakotr, Chalermkwan
    Lagerstedt, Anne-Sofie
    Pettersson, Ann
    Catestatin, vasostatin, cortisol, and pain assessments in dogs suffering from traumatic bone fractures.2017In: BMC Research Notes, ISSN 1756-0500, E-ISSN 1756-0500, Vol. 10, no 1, article id 129Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Traumatic bone fractures cause moderate to severe pain, which needs to be minimized for optimal recovery and animal welfare, illustrating the need for reliable objective pain biomarkers for use in a clinical setting. The objectives of this study were to investigate catestatin (CST) and vasostatin (VS) concentrations as two new potential biomarkers, and cortisol concentrations, scores of the short form of the Glasgow composite measure pain scale (CMPS-SF), and visual analog scale (VAS) in dogs suffering from traumatic bone fractures before and after morphine administration in comparison with healthy dogs.

    METHODS: Fourteen dogs with hind limb or pelvic fractures and thirty healthy dogs were included. Dogs with fractures were divided into four groups according to analgesia received before participation. Physical examination, CMPS-SF, pain and stress behavior VAS scores were recorded in all dogs. Saliva and blood were collected once in healthy dogs and in dogs with fractures before and 35-70 min after morphine administration. Blood samples were analyzed for CST, VS, and cortisol. Saliva volumes, however, were insufficient for analysis.

    RESULTS: Catestatin and cortisol concentrations, and CMPS-SF, and VAS scores differed significantly between dogs with fractures prior to morphine administration and healthy dogs. After morphine administration, dogs with fractures had significantly decreased CMPS-SF and VAS scores and, compared to healthy dogs, CST concentrations, CMPS-SF, and VAS scores still differed significantly. However, CST concentrations remained largely within the normal range. Absolute delta values for CST significantly correlated with delta values for CMPS-SF. Catestatin and cortisol did not differ significantly before and after morphine administration. Vasostatin concentrations did not differ significantly between groups.

    CONCLUSIONS: Catestatin and cortisol concentrations, CMPS-SF, and VAS scores differed significantly in the dogs with traumatic bone fractures compared to the healthy dogs. Morphine treatment partially relieved pain and stress according to the subjective but not according to the objective assessments performed. However, because of the large degree of overlap with normal values, our results suggest that plasma CST concentrations have a limited potential as a clinically useful biomarker for pain-induced stress.

  • 348. Srithunyarat, Thanikul
    et al.
    Höglund, Odd V
    Hagman, Ragnvi
    Olsson, Ulf
    Stridsberg, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemical endocrinology.
    Lagerstedt, Anne-Sofie
    Pettersson, Ann
    Catestatin, vasostatin, cortisol, temperature, heart rate, respiratory rate, scores of the short form of the Glasgow composite measure pain scale and visual analog scale for stress and pain behavior in dogs before and after ovariohysterectomy.2016In: BMC Research Notes, ISSN 1756-0500, E-ISSN 1756-0500, Vol. 9, article id 381Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The stress reaction induced by surgery and associated pain may be detrimental for patient recovery and should be minimized. The neuropeptide chromogranin A (CGA) has shown promise as a sensitive biomarker for stress in humans. Little is known about CGA and its derived peptides, catestatin (CST) and vasostatin (VS), in dogs undergoing surgery. The objectives of this study were to investigate and compare concentrations of CGA epitopes CST and VS, cortisol, body temperature, heart rate, respiratory rate, scores of the short form of the Glasgow composite measure pain scale (CMPS-SF) and visual analog scales (VAS) for stress and pain behavior in dogs before and after ovariohysterectomy.

    METHODS: Thirty healthy privately owned female dogs admitted for elective ovariohysterectomy were included. Physical examination, CMPS-SF, pain behavior VAS, and stress behavior VAS were recorded and saliva and blood samples were collected before surgery, 3 h after extubation, and once at recall 7-15 days after surgery. Dogs were premedicated with morphine and received carprofen as analgesia for 7 days during the postoperative period.

    RESULTS: At 3 h after extubation, CMPS-SF and pain behavior VAS scores had increased (p < 0.0001) and stress behavior VAS scores, temperature, respiratory rate (p < 0.0001), plasma CST concentrations (p = 0.002) had decreased significantly compared to before surgery. No significant differences were observed in the subjective and physiological parameters between before surgery and at recall, but plasma CST (p = 0.04) and serum cortisol (p = 0.009) were significantly lower at recall. Plasma VS, saliva CST, and heart rate did not differ significantly at any observed time.

    CONCLUSION: Study parameters for evaluating surgery-induced stress and pain changed in dogs subjected to ovariohysterectomy. To further evaluate CST and VS usefulness as pain biomarkers, studies on dogs in acute painful situations are warranted.

  • 349.
    Stahel, Anette
    University of Skövde, School of Life Sciences.
    1,25(OH)2D3 Initially Reduces TGFβ Activity in PC-3 Prostate Cancer Cells2008Independent thesis Advanced level (degree of Master (One Year)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    The vitamin D metabolite 1,25(OH)2D3 has long been known to inhibit growth of prostate cancer cells and this mainly through a VDR-mediated pathway controlling target gene expression, resulting in cell cycle arrest, apoptosis and differentiation. Another major way in which 1,25(OH)2D3 inhibits cell growth in prostate cancer is via membrane-initiated steroid signalling, which triggers activation of signal cascades upon steroid binding to a receptor complex, leading to induction of genes regulating cell growth, proliferation and apoptosis. The main prostate cancer inhibiting membrane-initiated route is the TGFβ signalling pathway, elicited by the protein TGFβ. In this experiment the activating effects of 1,25(OH)2D3 on TGFβ in prostate cancer cells, as well as two other important proteins downstream in this cascade, Smad2 and 3, were investigated. PC-3 cells were incubated for 3, 5, 10, 30 and 60 minutes as well as 38 hours both together with 1,25(OH)2D3 of the concentrations 10-10 and 10-7 M and without. As the downstream cascade protein JNK is a known activator of Smad2/3, this procedure was also repeated with a JNK inhibitor. An ELISA assay scanning for activated TGFβ was then performed on supernatants from the cells treated without JNK inhibitor. In addition, a Western Blot scanning for activated Smad2 and 3 was performed on supernatants from all groups of treatment. The analysis of the result values showed that 10-10 M 1,25(OH)2D3 significantly lowered the content of active TGFβ in PC-3 cells within 3 and 5 minutes. Unfortunately the Western Blot was unsuccessful and needs therefore be repeated.

  • 350.
    Stahel, Anette
    University of Skövde, School of Life Sciences.
    24,25(OH)2D3 and Regulation of Catalase Activity in LNCaP Prostate Cancer Cells: A Study of Long-term Effects2008Student thesis
    Abstract [en]

    The vitamin D metabolite 1,25(OH)2D3 has long been known to inhibit growth of prostate cancer cells and this has been attributed to a VDR-mediated pathway controlling target gene expression, resulting in cell cycle arrest, apoptosis and differentiation. New research has shown that another vitamin D metabolite, 24,25(OH)2D3, inhibits proliferation of prostate cancer cells as well, more specifically, cells of the line LNCaP. It is not clear exactly how 24,25(OH)2D3 exerts this cancer growth inhibition but it has been shown that it is to some extent regulated via G protein coupled signalling pathways. Catalase is a haem-containing redox enzyme found in the majority of animal cells, plant cells and aerobic microorganisms. This enzyme is very important because it prevents excessive accumulation of the strongly oxidizing agent H2O2 which otherwise can do damage to the cells. Because of this preventive effect of catalase, important cellular processes which generate H2O2 as by-product can proceed safely. Biochemical analysis of catalase has shown that it binds endogenously to 24,25(OH)2D3. The fact that 24,25(OH)2D3 has anti-proliferative effects on prostate cancer cells combined with the fact that it binds to catalase generates the hypothesis that this binding interferes with the essential task of catalase to keep the cell free from accumulation of destructive H2O2, and by means of this interference induces apoptosis. Finding out about the cancer growth inhibiting mechanism behind each vitamin D metabolite is important and may be a lead in the search for a new, better treatment of prostate cancer. This is a follow-up to an earlier study, and the specific aim of this project was to find out if and in what way 24,25(OH)2D3 affects the enzymatic activity of catalase in LNCaP cells during long-term treatment (up to 48 hours). In this experiment LNCaP cells were incubated for 48 hours together with 24,25(OH)2D3 of the concentration 10-8 M, then a catalase assay was performed on the cells including fluorescence-mediated measuring of catalase activity in both treated and untreated cells. The analysis of the result values showed that despite of the rather high dose used, 24,25(OH)2D3 has no statistically significant effect on catalase activity in cells of the line LNCaP, regardless of time.

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