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  • 301.
    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.

  • 302. 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.

  • 303.
    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.

  • 304.
    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.

  • 305.
    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.

  • 306. 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.

  • 307.
    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.

  • 308.
    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.

  • 309.
    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.

  • 310.
    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.

  • 311.
    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.

  • 312. 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.

  • 313. 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.

  • 314.
    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.

  • 315.
    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.

  • 316.
    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.

  • 317.
    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.

  • 318.
    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.

  • 319.
    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.

  • 320.
    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.

  • 321.
    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.

  • 322.
    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.))
  • 323.
    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.

  • 324. 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)
  • 325.
    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.

  • 326.
    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.

  • 327. 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.

  • 328. 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.

  • 329.
    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.

  • 330.
    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.

  • 331.
    Staiger, E. A.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Cornell Univ, Dept Anim Sci, Ithaca, NY 14853 USA..
    Almén, M. S.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Promerova, M.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Max Planck Inst Sci Human Hist, Dept Archaeogenet, D-07745 Jena, Germany..
    Brooks, S.
    Univ Florida, Dept Anim Sci, Gainesville, FL 32611 USA..
    Cothran, E. G.
    Texas A&M Univ, Coll Vet Med & Biomed Sci, Dept Vet Integrat Biosci, College Stn, TX 77843 USA..
    Imsland, F.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Fegraeus, K. Jaderkvist
    Swedish Univ Agr Sci, Dept Anim Breeding & Genet, SE-75007 Uppsala, Sweden..
    Lindgren, G.
    Swedish Univ Agr Sci, Dept Anim Breeding & Genet, SE-75007 Uppsala, Sweden..
    Yeganeh, H. Mehrabani
    Univ Tehran, Dept Anim Sci, Tehran 54500, Iran..
    Mikko, S.
    Swedish Univ Agr Sci, Dept Anim Breeding & Genet, SE-75007 Uppsala, Sweden..
    Vega-Pla, J. L.
    Cria Caballar Fuerzas Armadas, Lab Invest Aplicada, Cordoba 14080, Spain..
    Tozaki, T.
    Lab Racing Chem, Genet Anal Dept, Utsunomiya, Tochigi 3200851, Japan..
    Rubin, Carl-Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Andersson, Leif
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Texas A&M Univ, Coll Vet Med & Biomed Sci, Dept Vet Integrat Biosci, College Stn, TX 77843 USA.;Swedish Univ Agr Sci, Dept Anim Breeding & Genet, SE-75007 Uppsala, Sweden..
    The evolutionary history of the DMRT3 'Gait keeper' haplotype2017In: Animal Genetics, ISSN 0268-9146, E-ISSN 1365-2052, Vol. 48, no 5, p. 551-559Article in journal (Refereed)
    Abstract [en]

    A previous study revealed a strong association between the DMRT3:Ser301STOP mutation in horses and alternate gaits as well as performance in harness racing. Several follow-up studies have confirmed a high frequency of the mutation in gaited horse breeds and an effect on gait quality. The aim of this study was to determine when and where the mutation arose, to identify additional potential causal mutations and to determine the coalescence time for contemporary haplotypes carrying the stop mutation. We utilized sequences from 89 horses representing 26 breeds to identify 102 SNPs encompassing the DMRT3 gene that are in strong linkage disequilibrium with the stop mutation. These 102 SNPs were genotyped in an additional 382 horses representing 72 breeds, and we identified 14 unique haplotypes. The results provided conclusive evidence that DMRT3: Ser301STOP is causal, as no other sequence polymorphisms showed an equally strong association to locomotion traits. The low sequence diversity among mutant chromosomes demonstrated that they must have diverged from a common ancestral sequence within the last 10 000 years. Thus, the mutation occurred either just before domestication or more likely some time after domestication and then spread across the world as a result of selection on locomotion traits.

  • 332.
    Staiger, Elizabeth Ann
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Cornell Univ, Dept Anim Sci, Ithaca, NY 14853 USA.
    Bellone, Rebecca R.
    Univ Calif Davis, Dept Populat Hlth & Reprod, Vet Genet Lab, Davis, CA 95616 USA..
    Sutter, Nathan B.
    La Sierra Univ, Dept Biol, Riverside, CA USA..
    Brooks, Samantha A.
    Univ Florida, Dept Anim Sci, POB 110910, Gainesville, FL 32611 USA..
    Morphological Variation in Gaited Horse Breeds2016In: Journal of Equine Veterinary Science, ISSN 0737-0806, E-ISSN 1542-7412, Vol. 43, p. 55-65Article in journal (Refereed)
    Abstract [en]

    Gaited horses, renowned for their smooth gaits, are anecdotally noted to have proportionally longer hind limbs than nongaited breeds of the same height. However, gaited horses perform a wide spectrum of different gaits that we hypothesize may require diverse skeletal adaptations. To investigate the contribution of morphology to gait ability, we collected body measurements from gaited and nongaited individual animals and principal component analysis was conducted on 32 body measures for a set of 1,682 horses. Principal component (PC) 1 captured 65.3% of the trait variance, whereas PC2 comprised 6.6% and PC3 3.2% of variance in the data set. All body measures correlated positively with PC1 which quantifies a horse's overall body size. In contrast, PC2 quantifies body thickness. Principal component 3 represents a pattern primarily involving skull thickness and lower limb length. Because of the presence of sexual dimorphism and unequal sampling across sexes, we generated a pruned data set of 432 individuals with equal numbers of gaited and nongaited horses within each sex class. Analysis of variance and pairwise correlations were conducted to identify differences in the PC scores and measurements (normalized by wither height) due to sex, gait phenotype, breed, and age. After accounting for these fixed effects, gaited horses were significantly different from nongaited horses in PC2 and PC3 (P <. 0001). Comparisons of individual measurements demonstrate that gaited horses have smaller eye and jaw widths, proportionally longer front limb segments and thinner lower limb circumferences (P <. 05). This is the first study to identify different proportions in the front limb segments associated with gait.

  • 333.
    Stanezai, S.
    et al.
    Malmö University.
    Sahlen, E.
    Malmö University.
    El-Schich, Z.
    Fridberg, Marie
    Kristianstad University, Research environment Learning in Science and Mathematics (LISMA). Kristianstad University, School of Education and Environment, Avdelningen för Naturvetenskap.
    Fredriksson, G. N.
    Lund University.
    Anagnostaki, L.
    Skåne University Hospital.
    Tassidis, Helena
    Kristianstad University, School of Education and Environment, Avdelningen för Naturvetenskap. Kristianstad University, Research environment Man & Biosphere Health (MABH).
    Persson, L.
    Lund University.
    Gjorloff Wingren, Anette
    Malmö University.
    Higher intensity of Low Molecular Weight Protein Tyrosine Phosphatase/ ACP-1 in survivors of patients diagnosed with Diffuse Large B Cell Lymphoma (DLBCL) compared to non-survivors2016In: Austin Biology, no 2, article id 1009Article in journal (Refereed)
    Abstract [en]

    Adult Diffuse Large B Cell Lymphoma (DLBCL) is a heterogeneous form of hematopoietic cancer and difficult to treat. In order to find a better diagnostic indication for the disease, we analyzed Low Molecular Weight Protein Tyrosine Phosphatase (LMWPTP) that in humans is encoded by the ACP1 gene. LMWPTP is an enzyme shown to counteract Protein Tyrosine Kinases (PTK) and was suggested to be a negative growth factor regulator. However, the 18 kDa PTP can also have a positive effect on cell growth and proliferation, indicating a controversial role in the tumorigenic process. LMWPTP exists in different isoforms which are electrophoretically, kinetically and immunologically distinct. We have studied two subgroups of DLBCL consisting of a Germinal Center B cell like (GCB) and a non-Germinal Center B cell like (non-GCB) group. The two subgroups have been defined by gene-expressing profiling and are associated with differential outcome. The expression levels of LMWPTP protein was compared and showed significant differences between the GCB and non- GCB subgroups (p=0.012). Interestingly, when the samples were divided into survivors and non-survivors, and thereafter analyzed for LMWPTP expression, the samples from patients with a higher survival rate showed increased staining intensity, whereas the samples from patients with lower intensity of LMWPTP did not survive the disease (p=0.001). In conclusion, we have shown that DLBCL patients with worse outcome express LMWPTP with a lower intensity, suggesting a tumor suppressor role for this form of the enzyme.

  • 334.
    Stedt, Johan
    et al.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Biology and Environmental Science.
    Bonnedahl, Jonas
    Kalmar County Hospital;Uppsala University.
    Hernandez, Jorge
    Uppsala University.
    Waldenström, Jonas
    Linnaeus University, Faculty of Health and Life Sciences, Department of Biology and Environmental Science.
    McMahon, Barry J.
    University College Dublin, UK.
    Tolf, Conny
    Linnaeus University, Faculty of Health and Life Sciences, Department of Biology and Environmental Science.
    Olsen, Björn
    Uppsala University.
    Drobni, Mirva
    Uppsala University;Östersund Hospital.
    Carriage of CTX-M type extended spectrum beta-lactamases (ESBLs) in gulls across Europe2015In: Acta Veterinaria Scandinavica, ISSN 0044-605X, Vol. 57, article id 74Article in journal (Refereed)
    Abstract [en]

    Background: Extended spectrum beta-lactamases (ESBLs), a group of enzymes conferring resistance to third generation cephalosporins have rapidly increased in Enterobacteriacae and pose a major challenge to human health care. Resistant isolates are common in domestic animals and clinical settings, but prevalence and genotype distribution varies on a geographical scale. Although ESBL genes are frequently detected in bacteria isolated from wildlife samples, ESBL dissemination of resistant bacteria to the environment is largely unknown. To address this, we used three closely related gull species as a model system and collected more than 3000 faecal samples during breeding times in nine European countries. Samples were screened for ESBL-producing bacteria, which were characterized to the level of ESBL genotype groups (SHV, TEM), or specific genotypes (CTX-M). Results: ESBL-producing bacteria were frequently detected in gulls (906 of 3158 samples, 28.7 %), with significant variation in prevalence rates between countries. Highest levels were found in Spain (74.8 %), The Netherlands (37.8 %) and England (27.1 %). Denmark and Poland represented the other extreme with no, or very few positive samples. Genotyping of CTX-M isolates identified 13 different variants, with bla(CTX-M-1) and bla(CTX-M-14) as the most frequently detected. In samples from England, Spain and Portugal, blaCTX-M-14 dominated, while in the rest of the sampled countries blaCTX-M-1 (except Sweden where bla(CTX-M-15) was dominant) was the most frequently detected genotype, a pattern similar to what is known from studies of human materials. Conclusions: CTX-M type ESBLs are common in the faecal microbiota from gulls across Europe. The gull ESBL genotype distribution was in large similar to published datasets from human and food-production animals in Europe. The data suggests that the environmental dissemination of ESBL is high from anthropogenic sources, and widespread occurrence of resistant bacteria in common migratory bird species utilizing urban and agricultural areas suggests that antibiotic resistance genes may also be spread through birds.

  • 335.
    Stillfors, Caroline
    Örebro University, School of Health and Medical Sciences.
    Ultraljudsscreening av bukaortaaneurysm: precision och reproducerbarhet2008Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [sv]

    Abdominellt aortaaneurysm (AAA) är en sjukdom som främst drabbar äldre män. Sjukdomen är förknippat med en mycket hög dödlighet. Det är viktigt att patienterna fångas upp under den latenta delen av sjukdomsförloppet (före ruptur), och erbjuds behandling. En hälsoundersökning (screening) av patienter i riskzonen skulle kunna sänka den AAA-relaterade mortaliteten. För denna typ av screening används ultraljud. Ofta är det läkare som utför undersökningarna men med dagens läkarbrist behöver man tänka om. Denna litteraturstudie undersöker om screening för AAA kan sänka mortaliteten i sjukdomen, men också precisionen och reproducerbarheten hos ultraljud som undersökningsmetod och om annan vårdpersonal kan utföra screeningen. Resultaten visar på ultraljudets höga precision och reproducerbarhet. Användarvänligheten gör att annan vårdpersonal efter adekvat utbildning med fördel kan utföra undersökningen. Screening för AAA sänker dramatiskt dödligheten i sjukdomen. Ytterligare forskning behövs kring screening för AAA hos andra riskgrupper, samt kring de patofysiologiska orsakerna bakom utveckling, expansion och ruptur.

  • 336. Strage, Emma M
    et al.
    Sundberg, Mårten
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Holst, Bodil S
    Andersson Franko, Mikael
    Ramström, Margareta
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Fall, Tove
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology.
    Lewitt, Moira
    Effect of insulin treatment on circulating insulin-like growth factor I and IGF-binding proteins in cats with diabetes mellitus.2018In: Journal of Veterinary Internal Medicine, ISSN 0891-6640, E-ISSN 1939-1676, Vol. 32, no 5, p. 1579-1590Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Insulin-like growth factor-I (IGF-I) is used to screen for acromegaly in diabetic cats. In humans, most circulating IGF-I forms ternary complexes (TC) with IGF-binding protein (IGFBP-3) and an acid-labile subunit. Compared to humans, the amount of TC in cats is more variable. Insulin-like growth factor-I concentrations are reported to increase during insulin treatment, more rapidly in cats achieving remission.

    OBJECTIVES: To investigate (i) factors associated with circulating IGF-I concentrations, including IGFBP-profiles (ii) effect of insulin treatment on IGF-I concentrations and (iii) IGF-I as prognostic marker of diabetes mellitus remission.

    ANIMALS: Thirty-one privately owned diabetic cats of which 24 were followed 1 year, and 13 healthy cats.

    METHODS: Prospective study. Serum insulin, IGF-I, glucose, and fructosamine concentrations were measured. IGF-binding forms were determined by chromatography in 14 diabetic and 13 healthy cats; and IGF-I, IGF-II, IGFBP-3, and IGFBP-5 by mass spectrometry in 3 cats achieving remission.

    RESULTS: Insulin-like growth factor-I median (interquartile range) before start of insulin treatment was 300 (160-556) ng/mL. Insulin-like growth factor-I was positively associated with TC (P < .0001) and endogenous insulin (P = .005) and negatively associated with fructosamine (P < .0001). Median IGF-I was higher 2-4 weeks after start of insulin treatment compared with baseline (300 versus 670 ng/mL, P = .0001) and predicted future remission (P = .046). In cats that went into remission, the amount of TC and IGFBP-3 increased, suggesting increase in IGF-I is dependent on TC formation.

    CONCLUSIONS: Insulin treatment should be accounted for when interpreting IGF-I in diabetic cats. Insulin-like growth factor-I 2-4 weeks after initiation of insulin treatment shows promise as prognostic marker for remission in diabetic cats.

  • 337.
    Strand, Magnus
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Estrogen signaling in stroke: genetic and experimental studies2007Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Stroke is a common and multifactorial disease influenced by genetic and environmental risk factors. It is a highly heterogeneous entity consisting of two main types, ischemic (80%) and hemorrhagic (20%) stroke. The most common form of hemorrhagic stroke is intracerebral hemorrhage (ICH). Ischemic stroke mainly results from thrombotic or embolic events, while ICH is caused by the rupture of an artery in the brain.

    The mean age of first-ever stroke is 75 years (73 vs. 78 years, for men and women, respectively) and the age-specific stroke incidence is higher for men as compared to women, suggesting that hormonal factors confer protection. A large body of experimental and observational studies shows that estrogens exert beneficial effects in the cardiovascular system. However, large, recent, clinical randomized trials have failed to demonstrate a lower risk of stroke with hormone replacement therapy (HRT) in elderly postmenopausal women. It is possible that HRT may only protect a subgroup of women. Here, genetic predisposition might be involved. Stroke incidence is 50% higher in northern compared to southern Sweden, suggesting a genetic predisposition in this population. This relatively homogeneous population displays founder effects, making it well suited for genetic studies. Since 1985, the MONICA and VIP projects have conducted large-scale cardiovascular health surveys in this population. Information about conventional stroke risk determinants and also DNA have been collected, and two prospective, nested case-referent cohorts (113 cases and 226 controls; 275 cases and 549 controls) have been sampled.

    To investigate whether genes of the estrogen signaling system may be important in stroke development, we performed genetic association studies, including specific functional single nucleotide polymorphisms in the genes for estrogen receptor alpha (ERα, ESR1), and its target genes osteoprotegerin (OPG, TNFRS11B) and interleukin-6 (IL-6, IL6). We found a significant association between the common c.454-397T/T genotype in ESR1 and ICH, remaining after adjustments for conventional stroke risk factors. The c.454-397T/T genotype also associated with increased systolic (SBP) and diastolic blood pressure (DBP). The combination of c.454- 397T/T and either hypertension, increased SBP, or increased DBP boosted this association substantially and significant synergistic effects on ICH risk between this genotype and increased blood pressure were demonstrated. In a second study, we found a similar association between the common OPG-1181C/C genotype and ICH.

    Cognitive impairments, including spatial memory and learning deficiencies, are common after stroke. Estrogens improve cognitive functions, including memory and learning processes, in postmenopausal women and ovariectomized rodents. Post-ischemic housing of rats in an enriched environment (EE) improves recovery of spatial memory and learning impairments. Both estrogen and EE induce neuroplasticity in the hippocampus. We hypothesized that 17β- estradiol combined with EE would accelerate recovery after experimental focal brain ischemia in ovariectomized rats and that such improvements could be related to expression of nerve growth factor-induced gene A (NGFI-A) in the hippocampus. Five to six weeks after middle cerebral artery occlusion, 17β-estradiol–treated rats housed in an EE showed significant improvements in cognitive function (i.e., shorter latency and path in the Morris water maze task) and significantly higher NGFI-A mRNA expression in bilateral cornu ammonis 1 (CA1) and ipsilateral dentate gyrus (DG) compared to placebo-treated animals in EE.

    In conclusion, we present evidence for the association between polymorphic variants in the ESR1 and TNFRS11B genes and ICH and show that 17β-estradiol in combination with EE accelerates cognitive functions in a rat stroke model, putatively through upregulation of NGFI-A in hippocampal subregions. These findings may contribute to an increased understanding of the underlying genetic etiology of ICH and may be informative for the primary prevention of this disease. They also provide hope for 17β-estradiol combined with early environmental enrichment as a novel therapeutic option following ischemic stroke.

  • 338.
    Stridsberg, Mats
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemical endocrinology.
    Pettersson, Ann
    Hagman, Ragnvi
    Westin, Christoffer
    Höglund, Odd
    Chromogranins can be measured in samples from cats and dogs2014In: BMC Research Notes, ISSN 1756-0500, E-ISSN 1756-0500, Vol. 7, article id 336Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Methods for objective evaluation of stress in animals are important, but clinically difficult. An alternative method to study the sympathetic activity may be to investigate Chromogranin A (CGA), Chromogranin B (CGB) and Secretogranin II (SG2). The aim of this study was to investigate the cross-reactivity of CGA, CGB and SG2 between man, cat and dog and to explore possibilities to measure these proteins in samples from cats and dogs.

    RESULTS: Adrenal gland extracts from feline and canine species were measured by region-specific radioimmunoassays in different dilution steps to explore possible inter species cross reactivity. High cross reactivity was found for cats in the CGA17-38, CGA324-337, CGA361-372, CGB and SG2 assays. High cross reactivity was found for dogs in the CGA17-38, CGA361-372, CGB and SN assays. The method measuring the intact CGA was not useful for measurements in cats and dogs.

    CONCLUSIONS: Region-specific assays measuring defined parts of CGA, CGB and SG2 can be used for measurements in samples from cats and dogs. These results are promising and will allow for further studies of these proteins as possible clinical biomarkers in cats and dogs.

  • 339.
    Stroikin, Yuri
    Linköping University, Department of Clinical and Experimental Medicine, Experimental Pathology. Linköping University, Faculty of Health Sciences.
    Ageing-associated changes of lysosomal compartment: implications on cellular functions2007Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The lysosomal compartment is a major site for intracellular degradation. Lysosomal degradation of the cell’s own constituents, so-called autophagy, not only provides a cell with nutrients, but also removes damaged and potentially dangerous endogenous structures, thus securing intracellular homeostasis. On the other hand, lysosomes have been shown to be involved in the initial stages of apoptosis, and the protective effect of autophagy has been suggested to switch to cell death when excessive.

    Ageing-related changes of cellular structures result from damage caused by eactive oxygen species (ROS), which are an inevitable by-product of aerobic life. Intracellular turnover of compromised organelles and macromolecules, to which lysosomal degradation is a major contributor, does not function perfectly, even under favourable conditions. This inherent incompleteness of lysosomal degradation is responsible for the accumulation of a variety of nondegraded and functionally inefficient structures, which can be considered biological “garbage”. Biological “garbage” includes damaged non-degraded macromolecules and organelles, as well as intralysosomal non-degradable polymer-like structure called lipofuscin, or age pigment. Although accumulation of biological “garbage” has been suggested harmful, little is known about the mechanisms of its deleterious effects.

    To gain a better understanding of ageing-related changes of the lysosomal compartment and their influence on cell functions, we focused on studying: (1) the role of macroautophagy in the turnover of organelles and lipofuscin formation; (2) the role of biological “garbage” accumulation in the development of ageing-related changes and eventual death of growth-arrested, postmitotic-like cells; (3) the possible cell-protective effect of mitosis; (4) the influence of lipofuscin on cell survival during complete starvation; and (5) the effects of lipofuscin on lysosomal stability.

    As a model of induced biological “garbage” accumulation we used confluent human fibroblasts treated with the autophagy inhibitor 3-methyladenine (3MA). Alternatively, lysosomal degradation was suppressed by using the cysteine protease inhibitor leupeptin, or the cathepsin D inhibitor pepstatin A. As a cellular model of aged cells, we used lipofucsin-loaded human fibroblasts. Lipofuscin-loading was achieved by culturing confluent fibroblasts under hyperoxic conditions for 2-4 months. Using these in vitro models, the present study shows that: (1) inhibition of autophagy results in accumulation of lysosome-associated autofluorescent material and mitochondria with low membrane potential; (2) detrimental effect of biological “garbage” accumulation following inhibition of autophagy is prevented by continuous cell division; (3) lipofuscin-loaded cells are more resistant to starvation-induced cell death than control cells; (4) lysosomes of lipofuscinloaded fibroblasts are more resistant to the organelle-targeted stress then lysosomes of control cells.

    Based on the results of the present study we conclude that properly operating autophagic machinery plays a crucial role in preventing age-related changes associated with accumulation of biological “garbage”. We also suggest that continual proliferation is the natural mechanism by which cells cope with the accumulation of non-degradable material, employing mechanical dilution during the cell division. Finally, we introduce an idea of lipofuscin being a hormetic agent, and possibly possessing some lysosome-stabilising properties. Better understanding of the influence of the age-related accumulation of biological “garbage” on cellular functions may be helpful for future development of anti-ageing therapy and management of age-associated pathologies.

  • 340.
    Stroikin, Yuri
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Experimental Pathology. Linköping University, Faculty of Health Sciences.
    Mild, Hanna
    Linköping University, Department of Clinical and Experimental Medicine, Experimental Pathology. Linköping University, Faculty of Health Sciences.
    Johansson, Uno
    Linköping University, Department of Clinical and Experimental Medicine, Experimental Pathology. Linköping University, Faculty of Health Sciences.
    Roberg, Karin
    Linköping University, Department of Clinical and Experimental Medicine, Oto-Rhiono-Laryngology and Head & Neck Surgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Reconstruction Centre, Department of ENT - Head and Neck Surgery UHL.
    Öllinger, Karin
    Linköping University, Department of Clinical and Experimental Medicine, Experimental Pathology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Pathology and Clinical Genetics.
    Lysosome-targeted stress reveals increased stability of lipofuscin-containing lysosomes2008In: Age (Omaha), ISSN 0161-9152, E-ISSN 1574-4647, Vol. 30, no 1, p. 31-42Article in journal (Refereed)
    Abstract [en]

    Cellular ageing is associated with accumulation of undegradable intralysosomal material, called lipofuscin. In order to accelerate the lipofuscin-accumulation, confluent, growth arrested human fibroblasts were cultured under hyperoxic conditions. To provide a better insight into the effects of lipofuscin on cellular functions, we compared lysosomal stability in control and lipofuscin-loaded human fibroblasts under conditions of lysosome-targeted stress induced by exposure to either the lysosomotropic detergent MSDH or the redox-cycling quinone naphthazarin. We show that lysosomal damage, assessed by acridine-orange relocation, translocation of cathepsin D to the cytosol, and alkalinization of lysosomes is more pronounced in control than in lipofuscin-loaded fibroblasts. Finding that lysosomal integrity was less affected or even preserved in case of lipofuscin-loaded cells enables us to suggest that lipofuscin exerts lysosome-stabilizing properties.

  • 341.
    Ström Holst, Bodil
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Reproductive Biology in Uppsala (CRU). Swedish Univ Agr Sci, Dept Clin Sci, Box 7054, SE-75007 Uppsala, Sweden.
    Hagberg Gustavsson, Malin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Reproductive Biology in Uppsala (CRU).
    Johannisson, Anders
    Swedish Univ Agr Sci, Dept Clin Sci, Box 7054, SE-75007 Uppsala, Sweden.
    Hillström, Anna
    Swedish Univ Agr Sci, Univ Anim Hosp, Clin Pathol Lab, Box 7038, SE-75007 Uppsala, Sweden.
    Strage, Emma
    Swedish Univ Agr Sci, Univ Anim Hosp, Clin Pathol Lab, Box 7038, SE-75007 Uppsala, Sweden.
    Olsson, Ulf
    Swedish Univ Agr Sci, Unit Appl Stat & Math, Box 7032, SE-75007 Uppsala, Sweden.
    Axnér, Eva
    Swedish Univ Agr Sci, Dept Clin Sci, Box 7054, SE-75007 Uppsala, Sweden.
    Lilliehöök, Inger
    Swedish Univ Agr Sci, Dept Clin Sci, Box 7054, SE-75007 Uppsala, Sweden.
    Inflammatory changes during canine pregnancy2019In: Theriogenology, ISSN 0093-691X, E-ISSN 1879-3231, Vol. 125, p. 285-292Article in journal (Refereed)
    Abstract [en]

    Pregnancy is considered a pro-inflammatory state that requires physiologic adaptation of the immune system of the mother. The aim of the present study was to study inflammatory and hormonal changes during canine pregnancy. Studies included analyses of peripheral concentrations of the acute phase proteins fibrinogen and C-reactive protein (CRP), the hormones progesterone and insulin-like growth factor I (IGF-I), hemoglobin, and analyses of the total leukocyte numbers and expression of cell surface antigens. Twenty bitches were included in the present study; 12 pregnant bitches and eight nonpregnant control bitches that were followed during the corresponding phase of the oestrous cycle. Blood samples were collected at the day of optimal mating (day 0) and then on days 7, 14, 21, 28 and 42. Progesterone, IGF-I and CRP were analysed in serum and fibrinogen in EDTA plasma. Haematology and leukocyte expression of a panel of inflammation-associated adhesion molecules (CD 11a, CD 18 and CD 49d) were evaluated from EDTA blood. The data were analyzed as repeated-measures data, using a mixed model approach. Progesterone varied with time in both pregnant and control bitches, and IGF-I varied with time in pregnant bitches. Both fibrinogen and CRP increased significantly with time for the pregnant bitches, but no significant change was detected for the control bitches. Increases were seen from day 21. The hemoglobin concentration decreased significantly with time in both pregnant and non-pregnant bitches. The neutrophil and monocyte numbers increased significantly in pregnant but not in control bitches. Pregnancy induced increased granulocyte expression of cell surface marker CD 18, increased monocyte expression of CD 18 and CD 49d, and increased lymphocyte expression of CD 49d. In conclusion, we describe inflammatory changes during canine pregnancy that are manifested as increases in concentrations of CRP and fibrinogen, an increase in neutrophils and monocytes, and in activation of granulocytes, monocytes and lymphocytes. The changes should be taken into account when evaluating concentrations of APPS and WBC in bitches during pregnancy. A variation in IGF-I concentrations was detected during pregnancy.

  • 342.
    Ström, Jakob O.
    et al.
    Linköping University, Linköping, Sweden; County Council of Östergötland, Linköping, Sweden.
    Ingberg, Edvin
    Linköping University, Linköping, Sweden; County Council of Östergötland, Linköping, Sweden.
    Druvefors, Emma
    Ryhov County Hospital, County Council of Jönköping, Jönköping, Sweden.
    Theodorsson, Annette
    Linköping University, Linköping, Sweden; County Council of Östergötland, Linköping, Sweden.
    Theodorsson, Elvar
    Linköping University, Linköping, Sweden; County Council of Östergötland, Linköping, Sweden.
    The female menstrual cycle does not influence testosterone concentrations in male partners2012In: Journal of Negative Results in Biomedicine, ISSN 1477-5751, E-ISSN 1477-5751, Vol. 11, p. 1-7, article id 1Article in journal (Refereed)
    Abstract [en]

    Background: The time of ovulation has since long been believed to be concealed to male heterosexual partners. Recent studies have, however, called for revision of this notion. For example, male testosterone concentrations have been shown to increase in response to olfactory ovulation cues, which could be biologically relevant by increasing sexual drive and aggressiveness. However, this phenomenon has not previously been investigated in real-life human settings. We therefore thought it of interest to test the hypothesis that males' salivary testosterone concentrations are influenced by phases of their female partners' menstrual cycle; expecting a testosterone peak at ovulation.

    Methods: Thirty young, healthy, heterosexual couples were recruited. During the course of 30-40 days, the women registered menses and ovulation, while the men registered sexual activity, physical exercise, alcohol intake and illness (confounders), and obtained daily saliva samples for testosterone measurements. All data, including the registered confounders, were subjected to multiple regression analysis.

    Results: In contrast to the hypothesis, the ovulation did not affect the testosterone levels, and the resulting testosterone profile during the menstrual cycle was on the average flat. The specific main hypothesis, that male testosterone levels on the day of ovulation would be higher than day 4 of the cycle, was clearly contradicted by a type II error(β)-analysis (< 14.3% difference in normalized testosterone concentration; β = 0.05).

    Conclusions: Even though an ovulation-related salivary testosterone peak was observed in individual cases, no significant effect was found on a group level.

  • 343.
    Ström, Jakob O.
    et al.
    Linköping University Hospital, Linköping, Sweden.
    Theodorsson, Annette
    Linköping University Hospital, Linköping, Sweden.
    Theodorsson, Elvar
    Linköping University Hospital, Linköping, Sweden.
    Substantial discrepancies in 17beta-oestradiol concentrations obtained with three different commercial direct radioimmunoassay kits in rat sera2008In: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686, Vol. 68, no 8, p. 806-813Article in journal (Refereed)
    Abstract [en]

    The extensive use of oestrogen for contraception and amelioration of post-menopausal symptoms has made it the subject of substantial recent research efforts, and ovariectomized (ovx) rats treated with exogenous ovarial hormones are important when investigating the effects and mechanisms of oestrogen actions. The crucial need to control and monitor plasma levels of 17beta-oestradiol calls for accurate, precise and robust assay methods. The performance of direct radioimmunoassays (RIAs) in measurement of 17beta-oestradiol has been reported previously for human samples, but to our knowledge not for rat samples. In the current study, 552 serum samples from ovx, native and hormone-treated rats were used to compare the performance of three commercially manufactured direct RIAs from the companies DPC (Siemens Healthcare Diagnostics Inc., formerly Diagnostic Products Corporation), DSL (Diagnostic Systems Labs) and MPB (MP Biomedicals, formerly ICN Biomedicals). Substantial differences in results between the three assay methods were found when measuring serum 17beta-oestradiol concentrations. The following formulas describing the relation between the different methods were obtained using weighted Deming's orthogonal regression (based on pg/mL): DSL = 0.43*DPC+12.3, MPB = 2.1*DPC+84.7 and DSL = 4.8*MPB+22.2. Furthermore, a preceding diethyl ether extraction step of the serum appears to impair the performance of the RIAs in the present samples (based on pg/mL): DPC(ex) = 0.39*DPC(unex)+0.76, DSL(ex) = 0.32*DSL(unex)-1.7 and MPB(ex) = 0.22*MPB(unex)+1.4.

  • 344.
    Strömberg, Jessica
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    Sex and stress steroid modulation of GABA mediated chloride ion flux in rat CNS2007Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Background: Sex and stress steroids are metabolized to 3a-hydroxy-pregnane-steroid metabolites such as allopregnanolone (Allo) and tetrahydrodeoxycorticosterone (THDOC). Allo and THDOC are neuroactive steroids that are metabolized in the brain and act in brain as potent positive GABAA receptor function modulators. Allo as well as THDOC levels increase during stress. Allo has been associated with a number of symptoms and malfunctions such as impaired memory function and negative mood symptoms in a subgroup of individuals both for animals and humans. Pregnane steroids with 3b-hydroxy-configuration (3b-steroids) have been shown to reduce the Allo enhanced GABA effect.

    Aims: The aims for the present thesis were to investigate the effect of 3b-steroids on the GABA mediated GABAA receptor function in presence of positive GABAA receptor modulators. Further, the regional variances between the 3b-steroids as well as the mechanism of the effect were studied. Finally, the effect of stress steroid metabolites on the GABAA receptor function was investigated.

    Results: 3b-OH-5a-pregnane-20-one reduced the Allo enhanced GABA mediated chloride ion uptake into cortical microsacs. The 3b-isomer reduced the efficacy of Allo without shift the concentration response curve. It is therefore suggested that the 3b-isomer has a non-competitive effect. Further, it was shown that the 3b-isomer reduced the Allo effect in a selective way since the 3b-isomer did not interact with other positive modulators or with GABA itself. Five tested 3b-steroids reduced the Allo enhanced GABA mediated chloride ion uptake in cerebral cortex and hippocampus as well as the Allo prolongation on spontaneous inhibitory postsynaptic currents (sIPSCs) in preoptic nucleus. In cerebellum on the other hand the 3b-steroids showed to have weaker or no effect compared to the other tested regions. Interestingly, in absence of Allo, two of the 3b-steroids positively modulated the GABA stimulated GABAA receptor function. In absence of Allo, 5b-pregnane-3b,20(R)-diol increased the desensitization rate of current response. In contrast to the reducing effect on the Allo induced prolongation on sIPSCs, the effect of the 3b-steroid on GABA application, was not altered in presence of Allo. The mechanism of the 3b-steroid is therefore suggested being desensitization dependent in contrast to Allo, which has been suggested to decrease the GABA unbinding rate. In contrast to the enhanced effect of Allo, glucocorticoid metabolites reduced the GABA mediated chloride ion uptake in a concentration dependent way. The results in present thesis indicate that both sex and stress steroid metabolites interact with the GABAA receptor function. The knowledge that diversity of endogenous steroids interact with the GABAA receptor function is of importance for further understanding of different sex and stress steroid related symptoms and syndromes.

  • 345.
    Suarez Sipmann, Fernando
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Titrating Open Lung PEEP in Acute Lung Injury: A clinical method based on changes in dynamic compliance2008Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The recognition that supportive mechanical ventilation can also damage the lung, the so called ventilation induced lung injury (VILI), has revived the more than 40 year long debate on the optimal level of PEEP to be used. It is established that the prevention of VILI improves patient outcome and that PEEP exerts protective effects by preventing unstable diseased alveoli from collapsing. Therefore, the term “open lung PEEP” (OL-PEEP) has been introduced as the end-expiratory pressure that keeps the lung open after its collapse has been eliminated by an active lung recruitment manoeuvre. The determination of such an optimal level of PEEP under clinical circumstances is difficult and remains to be investigated.

    The aim of this study was to investigate the usefulness of breath by breath monitoring of dynamic compliance (Cdyn) as a clinical means to identify OL-PEEP at the bedside and to demonstrate the improvement in lung function resulting from its application.

    In a porcine lung lavage model of acute lung injury PEEP at maximum Cdyn during a decremental PEEP trial after full lung recruitment was related to the onset of lung collapse and OL-PEEP could be found 2 cmH2O above this level Ventilation at OL-PEEP was associated with improved gas exchange, efficiency of ventilation, lung mechanics and less than 5% collapse on CT scans. In addition, dead space, especially its portion related to alveolar gas changed characteristically during recruitment, PEEP titration and collapse thereby helping to identify OL-PEEP.

    The beneficial effects of OL-PEEP on lung function and mechanics was demonstrated in a porcine model of VILI. OL-PEEP improved lung function and mechanics when compared to lower or higher levels prior to or after lung recruitment. By using electrical impedance tomography it could be shown that PEEPs within the range of 14 to 22 cmH2O resulted in a similar redistribution of both ventilation and perfusion to the dorsal regions of the lung. OL-PEEP resulted in the best regional and global matching of ventilation and perfusion explaining the drastic improvements in gas exchange. Also regional compliance was greatly improved in the lower half of the lung as compared to all other situations.

    In ARDS patients OL-PEEP could be identified applying the same protocol. The physiological changes described could now be reproduced and maintained during a four hours study ventilation period in real patients at four study centres.

    In conclusion, the usefulness of dynamic compliance for identifying open lung PEEP during a decremental PEEP trial was demonstrated under experimental and clinical conditions. This PEEP should then be used as an essential part of any lung protective ventilation strategy. The impact of ventilating ARDS patients according to the principles described in these studies on outcome are currently being evaluated in an international randomized controlled trial.

  • 346.
    Sundh, Josefin
    et al.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Department of Respiratory Medicine, Faculty of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Ställberg, Björn
    Department of Public Health and Caring Science, Family Medicine and Preventive Medicine, Uppsala University, Uppsala, Sweden.
    Lisspers, Karin
    Department of Public Health and Caring Science, Family Medicine and Preventive Medicine, Uppsala University, Uppsala, Sweden.
    Kämpe, Mary
    Department of Medical Sciences, Respiratory Medicine and Allergology, Uppsala University, Uppsala, Sweden.
    Janson, Christer
    Department of Medical Sciences, Respiratory Medicine and Allergology, Uppsala University, Uppsala, Sweden.
    Montgomery, Scott
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Research Department of Epidemiology and Public Health, University College London, London, United Kingdom.
    Comparison of the COPD Assessment Test (CAT) and the Clinical COPD Questionnaire (CCQ) in a Clinical Population2016In: COPD: Journal of Chronic Obstructive Pulmonary Disease, ISSN 1541-2555, E-ISSN 1541-2563, Vol. 13, no 1, p. 57-65Article in journal (Refereed)
    Abstract [en]

    Introduction: The COPD Assessment Test (CAT) and the Clinical COPD Questionnaire (CCQ) are both clinically useful health status instruments. The main objective was to compare CAT and CCQ measurement instruments.

    Methods: CAT and CCQ forms were completed by 432 randomly selected primary and secondary care patients with a COPD diagnosis. Correlation and linear regression analyses of CAT and CCQ were performed. Standardised scores were created for the CAT and CCQ scores, and separate multiple linear regression analyses for CAT and CCQ examined associations with sex, age (≤ 60, 61-70 and >70 years), exacerbations (≥1 vs 0 in the previous year), body mass index (BMI), heart disease, anxiety/depression and lung function (subgroup with n = 246).

    Results: CAT and CCQ correlated well (r = 0.88, p < 0.0001), as did CAT ≥ 10 and CCQ ≥ 1 (r = 0.78, p < 0.0001). CCQ 1.0 corresponded to CAT 9.93 and CAT 10 to CCQ 1.29. Both instruments were associated with BMI < 20 (standardised adjusted regression coefficient (95%CI) for CAT 0.56 (0.18 to 0.93) and CCQ 0.56 (0.20 to 0.92)), exacerbations (CAT 0.77 (0.58 to 0.95) and CCQ 0.94 (0.76 to 1.12)), heart disease (CAT 0.38 (0.17 to 0.59) and CCQ 0.23 (0.03 to 0.43)), anxiety/depression (CAT 0.35 (0.15 to 0.56) and CCQ 0.41 (0.21 to 0.60)) and COPD stage (CAT 0.19 (0.05 to 0.34) and CCQ 0.22 (0.07 to 0.36)).

    Conclusions: CAT and CCQ correlate well with each other. Heart disease, anxiety/depression, underweight, exacerbations, and low lung function are associated with worse health status assessed by both instruments.

  • 347.
    Sund-Levander, Märtha
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Nursing Science. Linköping University, Faculty of Medicine and Health Sciences.
    Grodzinsky, Ewa
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in West Östergötland, Research & Development Unit in Local Health Care. National Board Forens Med, Linkoping, Sweden.
    Variation in Normal Ear Temperature2017In: The American journal of surgery, ISSN 0002-9629, E-ISSN 1538-2990, Vol. 354, no 4, p. 370-378Article in journal (Refereed)
    Abstract [en]

    Background: Variation in baseline ear temperature, taken in the unadjusted mode, has yet to be established in different age groups. Because normal body temperatures show large variations, the same may be expected for increased temperatures in fever. The aims were to study variations in normothermic body temperatures measured with an ear thermometer and to determine differences between actual and perceived body temperature during a febrile episode (referred to as difftemp) in apparently healthy children and adults. Methods: Ear temperature was measured once in 2,006 individuals (61.7% females): 683 children aged 2 and 4 years, 492 adolescents aged 10-18 years, 685 adults aged 19-65 years and 146 elderly aged 66-89 years. Difftemp was estimated as the difference between the individuals ear body temperature, measured in the present study, and the respondents reported temperature when feverish. Results: Mean ear temperature was 36.4 +/- 0.6 degrees C overall and in the child and adult groups. In adolescents, it was 36.5 +/- 0.5 degrees C, and in elderly, 36.1 +/- 0.5 degrees C. Temperature in men was 36.3 +/- 0.6 degrees C, and in women, 36.5 +/- 0.5 degrees C. Difftemp was 1.1 +/- 0.7 degrees C in adolescents, 1.5 +/- 0.7 degrees C in children and adults, and 1.6 +/- 0.7 degrees C in those amp;gt; 65 years. Conclusions: Ear body temperature is lower than traditionally reported and differs with age and sex. An individual difftemp of 1.0-1.5 degrees C along with malaise might indicate fever.

  • 348.
    Sundström, Elisabeth
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Imsland, Freyja
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Mikko, Sofia
    Wade, Claire
    Sigurdsson, Snaevar
    Pielberg, Gerli R
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Golovko, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Curik, Ino
    Seltenhammer, Monika H.
    Soelkner, Johann
    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.
    Andersson, Leif
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Copy number expansion of the STX17 duplication in melanoma tissue from Grey horses2012In: BMC Genomics, ISSN 1471-2164, E-ISSN 1471-2164, Vol. 13, p. 365-Article in journal (Refereed)
    Abstract [en]

    Background: Greying with age in horses is an autosomal dominant trait, associated with loss of hair pigmentation, melanoma and vitiligo-like depigmentation. We recently identified a 4.6 kb duplication in STX17 to be associated with the phenotype. The aims of this study were to investigate if the duplication in Grey horses shows copy number variation and to exclude that any other polymorphism is uniquely associated with the Grey mutation.

    Results: We found little evidence for copy number expansion of the duplicated sequence in blood DNA from Grey horses. In contrast, clear evidence for copy number expansions was indicated in five out of eight tested melanoma tissues or melanoma cell lines. A tendency of a higher copy number in aggressive tumours was also found. Massively parallel resequencing of the similar to 350 kb Grey haplotype did not reveal any additional mutations perfectly associated with the phenotype, confirming the duplication as the true causative mutation. We identified three SNP alleles that were present in a subset of Grey haplotypes within the 350 kb region that shows complete linkage disequilibrium with the causative mutation. Thus, these three nucleotide substitutions must have occurred subsequent to the duplication, consistent with our interpretation that the Grey mutation arose more than 2,000 years before present.

    Conclusions: These results suggest that the mutation acts as a melanoma-driving regulatory element. The elucidation of the mechanistic features of the duplication will be of considerable interest for the characterization of these horse melanomas as well as for the field of human melanoma research.

  • 349.
    Sundström, Gunnel
    Umeå University, Faculty of Medicine, Public Health and Clinical Medicine.
    Hyaluronan in normal and malignant bone marrow: a clinical and morphological study with emphasis on myelofibrosis2005Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Fibrosis in the bone marrow is usually denominated myelofibrosis and may contribute to impaired hematopoiesis. Myelofibrosis is seen both in malignant and non-malignant diseases.

    The normal microenvironment in the bone marrow consists of a heterogenous population of hematopoietic and non-hematopoietic stromal cells, their extracellular products and hematopoietic cytokines. The stromal cells produce a complex array of molecules, among others collagens and glycosaminoglycans (GAGs) of which hyaluronan (HYA) is the most abundant. Marrow fibrosis results from an increased deposition of collagens, which are polypeptides. Staining for reticulin, mostly composed of collagen type III, is the common way of visualizing myelofibrosis. HYA, like the collagens, is widely distributed in connective tissues. Little is known about the distribution of HYA in bone marrow.

    The aims of this thesis have been to determine how HYA is distributed in normal and malignant bone marrow, compared to reticulin staining, and to follow patients with chronic myeloproliferative diseases (CMPD) during two years treatment with anagrelide considering development of cellularity and fibrosis.

    In bone marrow biopsies from healthy volunteers, the controls, HYA was found in a pattern that was concordant with the reticulin staining.

    Comparing patients with different malignant diseases with and without bone marrow involvemen, HYA staining was found to be significantly stronger in both groups compared to the controls.

    The HYA scores were also significantly higher in the bone marrow of patients with de novo acute myeloid leukemia (AML), compared to the controls.

    There was a correlation between HYA and reticulin in the patients with de novo AML, and in the patients with different malignant diseases with and without bone marrow involvement as in the controls.

    Increase of HYA, reticulin and cellularity in the bone marrow of patients with CMPD after two years of treatment with anagrelide indicated progression of fibrosis. Anagrelide is a valuable drug for reduction of platelets but seems unable to stop progression of fibrosis and hypercellularity.

    HYA is an interesting molecule with properties not only contributing to the structure of extracellular matrix but also to cell signaling and behaviour, although the understanding of the detailed mechanisms is still incomplete.

  • 350.
    Suserud, Björn-Ove
    University of Borås, School of Health Science.
    Nurses man the Swedish response cars, can they replace the physician in the air ambulance service?2007Conference paper (Refereed)
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