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  • 151. Christel, S
    et al.
    Dopson, Mark
    Linnaeus University, Faculty of Health and Life Sciences, Department of Biology and Environmental Science.
    Vera, M
    Sand, W
    Herold, M
    Wilmes, P
    Buetti-Dinh, Antoine
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Pivkin, I
    Trötschel, C
    Poetsch, A
    Nygren, J
    Kubista, M
    Systems Biology of Acidophile Biofilms for Efficient Metal Extraction2015In: Biotechnologies in Mining Industry and Environmental Engineering / [ed] M. Zaki Mubarok, Siti Khodijah Chaerun, Wahyudin Prawira Minwal, Fadhli Muhammad and Killang Pratama, 2015, p. 312-315Conference paper (Refereed)
    Abstract [en]

    This European Union ERASysApp funded study will investigate one of the major drawbacks of bioleaching of the copper containing mineral chalcopyrite, namely the long lag phase between construction and inoculation of bioleaching heaps and the release of dissolved metals. In practice, this lag phase can be up to three years and the long time period adds to the operating expenses of bioheaps for chalcopyrite dissolution. One of the major time determining factors in bioleaching heaps is suggested to be the speed of mineral colonization by the acidophilic microorganisms present. By applying confocal microscopy, metatranscriptomics, metaproteomics, bioinformatics, and computer modeling the authors aim to investigate the processes leading up to, and influencing the attachment of three moderately thermophilic sulfur-and/or iron-oxidizing model species:Acidithiobacillus caldusLeptospirillum ferriphilum, and Sulfobacillus thermosulfidooxidans. Stirred tank reactors containing chalcopyrite concentrate will be inoculated with these species in various orders and proportions and the effects on the lag phase and rates of metal release will be compared. Meanwhile, confocal microscopy studies of cell attachment to chalcopyrite mineral particles, as well as metatranscriptomics and metaproteomics of the formed biofilms will further increase understanding of the attachment process and help develop a model thereof. By fulfilling our goal to decrease the length of the lag phase of chalcopyrite bioleaching heaps we hope to increase their economic feasibility and therefore, industrial interest in bioleaching as a sustainable technology.

  • 152.
    Christel, Stephan
    et al.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Biology and Environmental Science.
    Fridlund, Jimmy
    Linnaeus University, Faculty of Health and Life Sciences, Department of Biology and Environmental Science.
    Buetti-Dinh, Antoine
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Buck, Moritz
    Uppsala University.
    Watkin, Elizabeth L.
    Curtin University, Australia.
    Dopson, Mark
    Linnaeus University, Faculty of Health and Life Sciences, Department of Biology and Environmental Science.
    RNA transcript sequencing reveals inorganic sulfur compound oxidation pathways in the acidophile Acidithiobacillus ferrivorans2016In: FEMS Microbiology Letters, ISSN 0378-1097, E-ISSN 1574-6968, Vol. 363, no 7, article id fnw057Article in journal (Refereed)
    Abstract [en]

    Acidithiobacillus ferrivorans is an acidophile implicated in low-temperature biomining for the recovery of metals from sulfide minerals. Acidithiobacillus ferrivorans obtains its energy from the oxidation of inorganic sulfur compounds, and genes encoding several alternative pathways have been identified. Next-generation sequencing of At. ferrivorans RNA transcripts identified the genes coding for metabolic and electron transport proteins for energy conservation from tetrathionate as electron donor. RNA transcripts suggested that tetrathionate was hydrolyzed by the tetH1 gene product to form thiosulfate, elemental sulfur and sulfate. Despite two of the genes being truncated, RNA transcripts for the SoxXYZAB complex had higher levels than for thiosulfate quinone oxidoreductase (doxDA genes). However, a lack of heme-binding sites in soxX suggested that DoxDA was responsible for thiosulfate metabolism. Higher RNA transcript counts also suggested that elemental sulfur was metabolized by heterodisulfide reductase (hdr genes) rather than sulfur oxygenase reductase (sor). The sulfite produced as a product of heterodisulfide reductase was suggested to be oxidized by a pathway involving the sat gene product or abiotically react with elemental sulfur to form thiosulfate. Finally, several electron transport complexes were involved in energy conservation. This study has elucidated the previously unknown At. ferrivorans tetrathionate metabolic pathway that is important in biomining.

  • 153.
    Christensen, Kjeld
    et al.
    Örebro University Hospital.
    Kozarcanin, Huda
    Uppsala University.
    Nilsson Ekdahl, Kristina
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences. Uppsala University.
    Nilsson, Bo
    Uppsala University.
    Evidence of contact activation in patients suffering from ST-elevation myocardial infarction2016In: Thrombosis Research, ISSN 0049-3848, E-ISSN 1879-2472, Vol. 141, p. 158-162Article in journal (Refereed)
    Abstract [en]

    Introduction: Factor (F) XIIa is an attractive target for anticoagulation in arterial thrombosis. The aim of this study is to investigate the degree of involvement of the contact system in cardiac infarctions. Methods and patients: 165 patients suffering from ST-elevation myocardial infarction (STEMI) and 100 healthy controls were included in the study. Samples were drawn at admission before percutaneous intervention (PCI), 1-3 days post-percutaneous intervention (PCI) and, in one-third of the patients, 3 months after PCI. In order to investigate the degree of Factor XII (FXII) activation, changes in FXIIa/AT and FXIIa/C1INH complex levels were quantified by ELISA. Results: FXIIa/AT levels at admission (0.89 +/- 0.50; p < 0.01) were significantly higher than those in normal individuals (0.39 +/- 0.28), but the levels after 1-3 days (0.33 +/- 0.33; p < 0.05) were essentially normalized. In contrast, the FXII/C1INH levels at admission (1.40 +/- 0.72; p < 0.001) and after 1-3 days (0.83 +/- 0.59; p < 0.001) were both significantly higher than those in normal individuals (0.40 +/- 0.30). FXIIa/AT and FXIIa/C1INH complexes at admission (p < 0.001; p < 0.001) and after 1-3 days (p < 0.02; p < 0.001) were significantly different from those at 3 months. No significant differences were observed when the data were stratified for patency (open/closed culprit lesions). Conclusion: Both FXIIa/AT and FXIIa/C1INH complexes were significantly increased and reflected the activation of FXII in STEMI patients at admission. In particular, FXIIa/AT complex elevations support the hypothesis that clot propagation-mediated FXII activation had occurred, and this activation may be a target for anticoagulation in patients with cardiac infarction. Based on previous studies, the FXIIa/C1INH complex levels were primarily interpreted to reflex endothelial cell activation. (C) 2016 Published by Elsevier Ltd.

  • 154.
    Christerson, Ulrika
    et al.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Keita, Åsa, V
    Linköping University, Sweden.
    Winberg, Martin E.
    Linköping University, Sweden.
    Söderholm, Johan D.
    Linköping University, Sweden;County Council Östergötland, Sweden.
    Gustafson-Svärd, Christina
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Possible Involvement of Intracellular Calcium-Independent Phospholipase A(2) in the Release of Secretory Phospholipases from Mast Cells-Increased Expression in Ileal Mast Cells of Crohn's Disease2019In: Cells, E-ISSN 2073-4409, Vol. 8, no 7, p. 1-15, article id 672Article in journal (Refereed)
    Abstract [en]

    Increased activity of secretory phospholipases A(2) (sPLA(2)) type-II was previously observed in ileum of Crohn's disease (CD). Our aims were to explore the involvement of calcium-independent (i)PLA(2 beta) in the release of sPLA(2)s from the human mast cell (MC) line (HMC-1) and investigate expressions of cytosolic (c)PLA(2) alpha, iPLA(2)beta, sPLA(2)-IIA and sPLA(2)-V in MCs of CD ileum. The release of sPLA(2) was investigated in HMC-1 by immunocytochemistry and ELISA. The expression intensities of PLA(2)s in mucosal MCs, and the proportion of PLA(2)-positive MCs, were investigated in normal ileum and in ileum from patients with CD by immunohistochemistry. The calcium ionophore-stimulated release of sPLA(2)-IIA and sPLA(2)-V from HMC-1 was reduced by the iPLA(2)-inhibitor bromoenol lactone. All four PLA(2)s were detectable in mucosal MCs, both in normal ileum and in CD, but the proportion of iPLA(2)beta-containing mucosal MCs and the expression intensity of sPLA(2)-IIA was increased in CD. Results indicate that iPLA(2)beta is involved in the secretion of sPLA(2)s from HMC-1, and suggest that iPLA(2)beta-mediated release of sPLA(2) from intestinal MCs may contribute to CD pathophysiology. Ex vivo studies on isolated mucosal mast cells are however needed to clarify the precise role of MC PLA(2)s in the inflammatory processes of CD.

  • 155.
    Classon, Lisa
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Atypiskt terminalt komplementkomplex: Kvantifiering av in vivo-nivåer av atypiskt terminalt komplementkomplex under normala och patofysiologiska betingelser2018Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    The late steps of complement activation involves a cleavage of complement protein C5, to C5a and C5b, which initiates the formation of terminal complement complex (TCC). The final complex is referred to as the membrane-attack-complex (MAC) which forms cytotoxic pores in, inter alia, gram-negative bacteria. The formation of MAC can be inhibited by endogenous regulators and the TCC is then released as a soluble complex, sC5b-9, in plasma. In the degree project, another type of TCC was studied, which in previous studies had shown to form independently of C3 and C5 convertases when serum was acidified to pH <7.0 in vitro. The purpose of the study was to investigate whether this atypical TCC (aTCC) was formed in piglets, which in a model of meconium aspiration syndrome (MAS), received a reduced systemic pH in vivo. The purpose was also to establish an ELISA for analyzing aTCC. Sandwich ELISA, with monoclonal anti-C5a / C5a (desArg) (clone T13/9) as a capture antibody and monoclonal anti-C9 (clone aE11) as a detection antibody, was used to analyse aTCC in plasma samples from 18 MAS piglets, and in control samples consisting of pig serum acidified to pH 6.8 and 6.4 in vitro. The amount of aTCC in the control samples increased when the pH was lowered, but the content of aTCC in the plasma samples decreased over the course of the MAS study. When the relative change in aTCC was related to the final pH of the MAS pigs, a significant relationship could be seen (p = 0.02) which showed that a major change in the aTCC coincided with a lower final pH. aTCC were generally higher in plasma samples compared with control samples, which could be due to differences in plasma vs serum for aTCC or that the samples came from pigs of different age and weight. Lack of pig-specific standard and negative control as well as low signal to noise ratio contribute to sources of error for the analysis and this requires continued optimization.

  • 156.
    Cleland, Dougal
    et al.
    The University of Newcastle, Australia.
    Olsson, Gustaf D.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Karlsson, Björn C. G.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Nicholls, Ian A.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences. Uppsala University.
    McCluskey, Adam
    The University of Newcastle, Australia.
    Molecular dynamics approaches to the design and synthesis of PCB targeting molecularly imprinted polymers: interference to monomer-template interactions in imprinting of 1,2,3-trichlorobenzene2014In: Organic and biomolecular chemistry, ISSN 1477-0520, E-ISSN 1477-0539, Vol. 12, no 5, p. 844-853Article in journal (Refereed)
    Abstract [en]

    The interactions between each component of the pre-polymerisation mixtures used in the synthesis of molecularly imprinted polymers (MIP) specific for 1,2,3,4,5-pentachlorobenzene (1) and 1,2,3-trichlorobenzene (2) were examined in four molecular dynamics simulations. These simulations revealed that the relative frequency of functional monomer template (FM T) interactions was consistent with results obtained by the synthesis and evaluation of the actual MIPs. The higher frequency of 1 interaction with tri-methylstyrene (TMS; 54.7%) than 1 interaction with pentafluorostyrene (PFS; 44.7%) correlated with a higher imprinting factor (IF) of 2.1 vs. 1.7 for each functional monomer respectively. The higher frequency of PFS interactions with 2 (29.6%) than TMS interactions with 2 (1.9%) also correlated well with the observed differences in IF (3.7) of 2 MIPs imprinted using PFS as the FM than the IF (2,8) of 2 MIPs imprinted using TMS as the FM. The TMS-1 interaction dominated the molecular simulation due to high interaction energies, but the weaker TMS-2 resulted in low interaction maintenance, and thus lower IF values. Examination of the other pre-polymerisation mixture components revealed that the low levels of TMS-2 interaction was, in part, due to interference caused by the cross linker (CL) ethyleneglycol dimethylacrylate (EGDMA) interactions with TMS. The main reason was, however, attributed to MeOH interactions with TMS in both a hydrogen bond and perpendicular configuration. This positioned a MeOH directly above the it-orbital of all TMS for an average of 63.8% of MD2 creating significant interference to pi-pi stacking interactions between 2 and TMS. These findings are consistent with the deviation from the 'normal' molecularly imprinted polymer synthesis ratio of 1 : 4 : 20 (T : FM : CL) of 20 : 1 : 29 and 15 : 6 : 29 observed with 2 and TMS and PFS respectively. Our molecular dynamics simulations correctly predicted the high level of interference from other MIP synthesis components. The effect on PFS-1 interaction by MeOH was significantly lower and thus this system was not adversely affected.

  • 157.
    Cocha, Laura Romina
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Metodutveckling för prövning av lektiners påverkan på patogena svampar2015Independent thesis Basic level (professional degree), 180 HE creditsStudent thesis
  • 158.
    Comasco, Erika
    et al.
    Uppsala University.
    Vumma, Ravi
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Toffoletto, Simone
    Uppsala University.
    Johansson, Jessica
    Örebro University.
    Flyckt, Lena
    Karolinska institutet.
    Lewander, Tommy
    Örebro university.
    Oreland, Lars
    Uppsala university.
    Bjerkenstedt, Lars
    Strömstad Academy, Strömstad, Sweden.
    Andreou, Dimitrios
    Karolinska institutet.
    Söderman, Erik
    Karolinska institutet.
    Terenius, Lars
    Karolinska institutet.
    Agartz, Ingrid
    Karolinska institutet ; University of Oslo, Norway ; Diakonhjemmet Hospital, Oslo, Norway.
    Jönsson, Erik G
    Karolinska institutet ; University of Oslo, Norway.
    Venizelos, Nikolaos
    Örebro university.
    Genetic and Functional Study of L-Type Amino Acid Transporter 1 in Schizophrenia.2016In: Neuropsychobiology, ISSN 0302-282X, E-ISSN 1423-0224, Vol. 74, no 2, p. 96-103Article in journal (Refereed)
    Abstract [en]

    Schizophrenia involves neural catecholaminergic dysregulation. Tyrosine is the precursor of catecholamines, and its major transporter, according to studies on fibroblasts, in the brain is the L-type amino acid transporter 1 (LAT1). The present study assessed haplotype tag single-nucleotide polymorphisms (SNPs) of the SLC7A5/LAT1 gene in 315 patients with psychosis within the schizophrenia spectrum and 233 healthy controls to investigate genetic vulnerability to the disorder as well as genetic relationships to homovanillic acid (HVA) and 3-methoxy-4-hydroxyphenylglycol (MHPG), the major catecholamine metabolites in the cerebrospinal fluid (CSF). Moreover, the involvement of the different isoforms of the system L in tyrosine uptake and LAT1 tyrosine kinetics were studied in fibroblast cell lines of 10 patients with schizophrenia and 10 healthy controls. The results provide suggestive evidence of individual vulnerability to schizophrenia related to the LAT1 SNP rs9936204 genotype. A number of SNPs were nominally associated with CSF HVA and MHPG concentrations but did not survive correction for multiple testing. The LAT1 isoform was confirmed as the major tyrosine transporter in patients with schizophrenia. However, the kinetic parameters (maximal transport capacity, affinity of the binding sites, and diffusion constant of tyrosine transport through the LAT1 isoform) did not differ between patients with schizophrenia and controls. The present genetic findings call for independent replication in larger samples, while the functional study seems to exclude a role of LAT1 in the aberrant transport of tyrosine in fibroblasts of patients with schizophrenia.

  • 159.
    Cournia, Zoe
    et al.
    Academy of Athens, Greece.
    Allen, Toby W.
    University of California, USA ; RMIT University, Australia.
    Andricioaei, Ioan
    University of California, USA.
    Antonny, Bruno
    Université de Nice Sophia-Antipolis, France.
    Baum, Daniel
    Zuse Institute Berlin, Germany.
    Brannigan, Grace
    Rutgers University-Camden, USA.
    Buchete, Nicolae-Viorel
    University College Dublin, Ireland.
    Deckman, Jason T.
    University of California, USA.
    Delemotte, Lucie
    Temple University, USA.
    del Val, Coral
    University of Granada, Spain.
    Friedman, Ran
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Gkeka, Paraskevi
    Academy of Athens, Greece.
    Hege, Hans-Christian
    Zuse Institute Berlin, Germany.
    Hénin, Jérôme
    IBPC and CNRS, France.
    Kasimova,, Marina A.
    Université de Lorraine, France ; Lomonosov Moscow State University, Russia.
    Kolocouris, Antonios
    University of Athens, Greece.
    Klein, Michael L.
    Temple University, USA.
    Khalid, Syma
    University of Southampton, UK.
    Lemieux, M. Joanne
    University of Alberta, Canada.
    Lindow, Norbert
    Zuse Institute Berlin, Germany.
    Mahua, Roy
    University of California, USA.
    Selent, Jana
    Universitat Pompeu Fabra, Spain.
    Tarek, Mounir
    Université de Lorraine, France ; CNRS SRSMC, France.
    Tofoleanu, Florentina
    University College Dublin, Ireland.
    Stefano, Vanni
    Université de Nice Sophia-Antipolis, Greece.
    Sinisa, Urban
    Johns Hopkins University School of Medicine, USA.
    Wales, David J.
    University of Cambridge, UK.
    Smith, Jeremy C.
    Oak Ridge National Laboratory, USA.
    Bondar, Ana-Nicoleta
    Freie Universität Berlin, Germany.
    Membrane Protein Structure, Function, and Dynamics: a Perspective from Experiments and Theory2015In: Journal of Membrane Biology, ISSN 0022-2631, E-ISSN 1432-1424, Vol. 248, no 4, p. 611-640Article in journal (Refereed)
    Abstract [en]

    Membrane proteins mediate processes that are fundamental for the flourishing of biological cells. Membrane-embedded transporters move ions and larger solutes across membranes; receptors mediate communication between the cell and its environment and membrane-embedded enzymes catalyze chemical reactions. Understanding these mechanisms of action requires knowledge of how the proteins couple to their fluid, hydrated lipid membrane environment. We present here current studies in computational and experimental membrane protein biophysics, and show how they address outstanding challenges in understanding the complex environmental effects on the structure, function, and dynamics of membrane proteins.

  • 160.
    Cronin, Jennifer
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Behandling med eculizumab vid katastrofalt antifosfolipidsyndrom2018Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    Catastrophic antiphospholipidsyndrome (CAPS) is a rare but highly fatal condition characterized by thrombosis in multiple organs, often associated with a rapid progression of disease and serious complications for the patient. A rapid diagnosis and treatment is therefore a key to manage this condition. The conventional treatment, which consists of anticoagulation, steroids, plasma exchange and intravenous immunoglobulins, reduces mortality but CAPS is still associated with high mortality. To find the mechanism of how and why this condition evolves is therefore important. There has been progress to find out the pathogenesis and one clue appears to be the complement system. Therefore, a new type of treatment has been used in patients who have been diagnosed with antiphosphlipidsyndrome (APS) and have had a risk of developing CAPS, or have been diagnosed with definitive or probable CAPS. This treatment is aimed at inhibiting parts of the complement system and consists of a monoclonal antibody called eculizumab. Lately eculizumab has been used off label in patients diagnosed with CAPS and in patients that has been at risk of developing CAPS. The results of this treatment have been positive and have therefore been considered as a possible alternative for treating CAPS.

    The aim of this study was to evaluate if eculizumab can be an alternative to treat patients with CAPS and patients diagnosed with APS who have a risk of developing CAPS.

    In order to evaluate treatment with eculizumab in patients with CAPS, searches on cases were done in the database PubMed for reports of patients with CAPS or at risk of developing CAPS who have been treated with eculizumab. Eight reports with a total of ten cases were found and used in order to answer the hypothesis of this study.

    In the ten cases that were analyzed there was a clear connection between the treatment and the recovery. In both patients with CAPS and patients at risk of developing CAPS the treatment with eculizumab was considered of significant importance. Because of the rarity of this condition, every case makes significant impact into the understanding of this potentially fatal condition. For future new cases, the present report will stand as an important source for making decisions about treatment with eculizumab. With time and more cases with positive results eculizumab has the potential to become conventional treatment for CAPS.

  • 161.
    Dadarman, Mina
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Möjlig mekanism bakom antiinflammatorisk polymer, polyvinylalkoholkarbazat: Studier av apoptos och viabilitet i cellkultur2018Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
  • 162.
    Dagsberg, Jacob
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Förekomst av aviärt influensavirus bland vilda fåglar provtagna vid Ottenby fågelstation under 2017: Detektion och fylogenetisk analys av neuraminidas subtyp 6-virus2018Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    Avian influenza virus (AIV) is divided into subtypes based on two glycoproteins on its surface. Among birds there are 16 subtypes of hemagglutinin (H) and 9 subtypes of neuraminidase (N). Some H subtypes can mutate into highly pathogenic viruses and cause deadly infections. One such highly pathogenic virus was reported in northern Europe in 2017. Spread amongst highly pathogenic H5 is well mapped out. Reverse transcription followed by amplification in real time is used to detect neuraminidase in AIV, based on synthesis of complementary DNA, which gets amplified and detected using fluorescent probe. Sanger sequencing of neuraminidase coding gene segments is used to verify the results from RT-qPCR screening and analysing phylogenetic relationship. To contribute with knowledge about neuraminidase subtype 6, RT-qPCR analysis was used on 282 AIV positive samples from wild birds, sampled at Ottenby bird station in 2017. Gene segments coding for hemaglutinin and neuraminidase among viruses in N6 positive samples was sequenced to validate the N6-RT-qPCR analyses, determine H subtype and to analyse phylogenetic relationship among N6-sequences. The RT-qPCR resulted in 37 N6 positive samples where 26 of these was confirmed as N6 with traditional PCR and sequencing. AIV from the analyses occurred in subtype constellations of: 14 H1N6, 3 H3N6, 8 H4N6 and 1 H5N6. Three samples failed to give H subtype, three different samples gave no N6 sequence. Detected H5N6 was low pathogenic. The phylogenetic analysis showed that AIV N6 sequences from Ottenby, in tandem with sequences from GenBank, formed four genotypes. N6 sequences from two viruses sequenced in this study, associated with subtypes H3N6 and H1N6 formed genotype two, together with four H5N6, possibly high pathogenic viruses from Japan.

  • 163.
    Dahlberg, Mikaela
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Kan Mindfulness-Based Stress Reduction (MBSR) minska den upplevda smärtan hos patienter med kronisk ländryggsmärta?: En litteraturstudie med metaanalys2018Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    Introduction: Lower back pain is very common; approximately 60-65 percent of the population in the Nordic region will experience lower back pain during a twelve-month period. There is an increased interest in using mindfulness methods such as Mindfulness-Based Stress Reduction (MBSR) to treat different types of pain. The research and recommendations for mindfulness as treatment for chronic lower back pain is varying and there is a need for update of evidence in the field of diagnostics, treatment, rehabilitation and prevention for non-specific chronic pains. Purpose: To describe if MBSR is an effective way to reduce pain intensity in adults (18> years) with chronic lower back pain. Method: A literature review was conducted in PubMed to obtain relevant articles and a quality assessment was conducted on included articles. A meta-analysis was performed to get an overview of the average effect size between the groups. Results: A total of six randomized controlled trials (RCT) were included in the literature study with a total of 902 patients (men and women with some type of chronic lower back pain (CLBP)). In the studies the intervention group was MBRS and the control group was common care (UC, normal medical care) or a health education program. The outcome variable measured was the pain intensity and the meta-analysis estimated an effect size (SMD, standardized mean difference) of -0.611 with a heterogeneity of I ^ 2 = 92.5%. Discussion: An MBSR program preformed during eight weeks showed tendencies of being able to provide reduced pain intensity in patients with CLBP with an average effect size for the benefit of MBSR. The significant heterogeneity which was observed reduces the relevance of the find. Conclusions: There is limited evidence of whether MBSR can reduce pain intensity in patients with CLBP. Standardized research is required to determine more clearly the effects of an MBSR intervention in patients with CLBP.

  • 164.
    Dahlqvist, Zandra
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Torklagringstemperatur för gryn- och rundpipig ost: Att finna en gemensam torklagringstemperatur för gryn- och rundpipig ost 2016Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    Cheese making is an old method that originally has been used as a means to preserve milk. More than hundred types of cheeses are produced around the world, varying in bacterial cultures, pressing and ripening conditions. Grevé-, Herrgård- and Prästcheese are all examples of Swedish semi-hard cheeses. Prästcheese is dried and stored at 17-19 °C, while Grevé and Herrgård are stored at 10-12 °C. The aim of this study was to find a common dry-storage temperature for such cheeses. Selected properties such as weight loss and nutritional content of the cheeses at reference temperature (17-19 °C and 10-12 °C) were compared to cheeses stored in a common storage room at the temperature 15.0 ± 0.5 °C. The nutritional content was analysed by infrared spectroscopy using a FOSS MilkoScan FT120.

    The results showed a significant difference between experimental and reference cheeses weight losses for Präst 31%, Grevé 28% and Herrgård 28% (P <0.05), whereas no significant difference in weight loss was observed for Präst 17% and Herrgård 17% (P> 0.05). There was a significant difference in diameter between the experimental and reference cheeses (P <0.05). The diameter was significantly greater for cheeses that were stored at a higher temperature. There was no significant difference in the nutrient content for Präst 31 %, Präst 17%, 28%, Grevé 28 % and Grevé 17% (P> 0.05). For Herrgård 28%, there was a significant difference in the lactic acid concentration (P <0.05), but no significant difference in other nutrient content (P> 0.05). A final assessment is required when the cheeses are matured, by a sensory panel to conclude if the experimental cheeses are of a quality than can be accepted by the customer with regard to e.g. appearance, texture and taste.

  • 165.
    Danielsson, Micaela
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Bindningsmönster av aviärt influensa A-virus till mag-tarmkanalen hos andfåglar2018Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    Influenza A virus is a major human disease, with recurrent seasonal outbreaks that cause up to 500,000 deaths worldwide every year. The natural reservoir and home to most subtypes of the virus is wild water birds. To get a better understanding of how so many different viruses can infect wild birds, the binding pattern of the virus to the host can be studied with the virus histochemistry technique. The purpose of this work was to investigate the binding pattern of avian influenza virus, subtype H4, H9, H13 and H16, to gastrointestinal tract tissues from different species of ducks to see which cells and in what quantity these viruses bind to. The techniques that have been used are propagation of the virus by culturing embryonated chicken eggs, sucrose gradient purification, formalin inactivation and then fluorescein isothiocyanate (FITC) labeling. The titre of the virus was measured by hemagglutination assay, showing the result that the titre after harvesting eggs for H4 was: 256 HAU/100 μl, H9: 512 HAU/100 μl, H13: 384 HAU/100 μl and for H16: 768 HAU/100 μl. FITC-labeled virus titer was measured to H4: 15 360 HAU/100 μl, H9: 30 720 HAU/100 μl, H13: 163 840 HAU/100 μl and H16: 81 920 HAU/100 μl. Virus histochemistry was not performed and therefore the result of the binding pattern is still unknown and the question of this work unanswered with in the time limit of this thesis. What is expected from the result, however, is that subtype H4 and H9, common to found in birds ducks, will bind to epithelial cells in the gastrointestinal tract of ducks while subtype H16 and H13, which have only been found in isolate from ducks in a few cases, are not expected bind to the gastrointestinal tract of ducks to the same extent.

  • 166.
    Danielsson, Tom
    et al.
    Linnaeus University, Faculty of Social Sciences, Department of Sport Science.
    Schreyer, Hendrik
    Kalmar County Hospital, Sweden.
    Woksepp, Hanna
    Kalmar County Hospital, Sweden.
    Johansson, Therese
    Kalmar County Hospital, Sweden.
    Bergman, Patrick
    Linnaeus University, Faculty of Social Sciences, Department of Sport Science.
    Månsson, Alf
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Carlsson, Jörg
    Linnaeus University, Faculty of Health and Life Sciences, Department of Health and Caring Sciences. Kalmar County Hospital, Sweden.
    Two-peaked increase of serum myosin heavy chain-α after triathlon suggests heart muscle cell death2019In: BMJ Open Sport & Exercise Medicine, ISSN 2055-7647, Vol. 5, article id e000486Article in journal (Refereed)
    Abstract [en]

    Objective It has been suggested that the mechanism behind cardiac troponin elevation after strenuous exercise is passage through a cell membrane with changed permeability rather than myocardial cell death. We hypothesised that an increase of cardiac specific myosin heavy chain-alpha (MHC-α; 224 kDa compared with cardiac troponin T’s (cTnT) 37 kDa) could hardly be explained by passage through a cell membrane.

    Methods Blood samples were collected from 56 athletes (15 female, age 42.5±9.7, range 24–70 years) before, directly after and on days 1–8 after an Ironman. Biomarkers (C reactive protein (CRP), cTnT, creatinekinase (CK), MHC-α, myoglobin (MG), creatinine (C) and N-terminal prohormone of brain natriuretic peptide (NTproBNP) were measured.

    Results The course of MHC-α concentration (μg/L) was 1.33±0.53 (before), 2.57±0.78 (directly after), 1.51±0.53 (day 1), 2.74±0.55 (day 4) and 1.83±0.76 (day 6). Other biomarkers showed a one-peaked increase with maximal values either directly after the race or at day 1: cTnT 76 ±80 ng/L (12–440; reference<15), NT-proBNP 776±684 ng/L (92–4700; ref.<300), CK 68±55 μkat/L (5–280; ref.<1.9), MG 2088±2350 μg/L (130–17 000; ref.<72) and creatinine 100±20 μmol/L (74–161; ref.<100), CRP 49±23 mg/L(15–119; ref.<5).

    Conclusion MHC-α exhibited a two-peaked increase which could represent a first release from the cytosolic pool and later from cell necrosis. This is the first investigation of MHC-α plasma concentration afterexercise.

  • 167.
    Darreh-Shori, Taher
    et al.
    Karolinska Institutet.
    Vijayaraghavan, Swetha
    Karolinska Institutet.
    Aeinehband, Shahin
    Karolinska University Hospital Solna.
    Piehl, Fredrik
    Karolinska University Hospital Solna.
    Lindblom, Rickard P. F.
    Karolinska University Hospital Solna.
    Nilsson, Bo
    Uppsala University.
    Nilsson Ekdahl, Kristina
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences. Uppsala University.
    Långström, Bengt
    Uppsala University;Imperial College, UK;Odense University Hospital, University of Southern Denmark, Denmark.
    Almkvist, Ove
    Karolinska Institutet;Stockholm University.
    Nordberg, Agneta
    Karolinska Institutet;Karolinska University Hospital Huddinge.
    Functional variability in butyrylcholinesterase activity regulates intrathecal cytokine and astroglial biomarker profiles in patients with Alzheimer's disease2013In: Neurobiology of Aging, ISSN 0197-4580, E-ISSN 1558-1497, Vol. 34, no 11, p. 2465-2481Article in journal (Refereed)
    Abstract [en]

    Butyrylcholinesterase (BuChE) activity is associated with activated astrocytes in Alzheimer's disease brain. The BuChE-K variant exhibits 30%-60% reduced acetylcholine (ACh) hydrolyzing capacity. Considering the increasing evidence of an immune-regulatory role of ACh, we investigated if genetic heterogeneity in BuChE affects cerebrospinal fluid (CSF) biomarkers of inflammation and cholinoceptive glial function. Alzheimer's disease patients (n = 179) were BCHE-K-genotyped. Proteomic and enzymatic analyses were performed on CSF and/or plasma. BuChE genotype was linked with differential CSF levels of glial fibrillary acidic protein, S100B, interleukin-1 beta, and tumor necrosis factor (TNF)-alpha. BCHE-K noncarriers displayed 100%-150% higher glial fibrillary acidic protein and 64%-110% higher S100B than BCHE-K carriers, who, in contrast, had 40%-80% higher interleukin-1b and 21%-27% higher TNF-alpha compared with noncarriers. A high level of CSF BuChE enzymatic phenotype also significantly correlated with higher CSF levels of astroglial markers and several factors of the innate complement system, but lower levels of proinflammatory cytokines. These individuals also displayed beneficial paraclinical and clinical findings, such as high cerebral glucose utilization, low beta-amyloid load, and less severe progression of clinical symptoms. In vitro analysis on human astrocytes confirmed the involvement of a regulated BuChE status in the astroglial responses to TNF-alpha and ACh. Histochemical analysis in a rat model of nerve injury-induced neuroinflammation, showed focal assembly of astroglial cells in proximity of BuChE-immunolabeled sites. In conclusion, these results suggest that BuChE enzymatic activity plays an important role in regulating intrinsic inflammation and activity of cholinoceptive glial cells and that this might be of clinical relevance. The dissociation between astroglial markers and inflammatory cytokines indicates that a proper activation and maintenance of astroglial function is a beneficial response, rather than a disease-driving mechanism. Further studies are needed to explore the therapeutic potential of manipulating BuChE activity or astroglial functional status. (C) 2013 Elsevier Inc. All rights reserved.

  • 168.
    Davidsson, Mattias
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Är olika statiner ekvipotenta: en analys av kontemporär evidens inklusive farmakologi och läkemedelskemi2019Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    Background: Statins are among the most used drugs in Sweden. There are currently four statins available on the Swedish market; atorvastatin, simvastatin, pravastatin and rosuvastatin. Statins act by inhibiting 3-hydroxy-3-methylglutaryl-coenzyme-A reductase, also known as HMG-CoA-reductase. HMG-CoA-reductase is the rate-limiting enzyme of the cholesterol synthesis. Decreased hepatic cholesterol leads to increased low-density lipoprotein (LDL) clearance from plasma to liver cells. Having a high level of LDL cholesterol is potentially dangerous as it can lead to atherosclerosis and cardiovascular disease. Statins significantly reduce cardiovascular morbidity and mortality in patients with and without coronary heart disease.

    Purpose: The aim of this work was to investigate if there are any differences between the different statins according to contemporary evidence.

    Method: This is a literary analysis. Studies included were searched from PubMed. A total of five studies were included.

    Results: The result of this study indicates rosuvastatin to be most efficacious in lowering LDL cholesterol (LDL-C), triglycerides and total cholesterol. It also improved the high-density lipoprotein cholesterol (HDL-C) better than atorvastatin, simvastatin and pravastatin. Study 1 showed rosuvastatin to lower LDL-C with statistical significance (P<0.001) across dose ranges (10-40 mg) after 12 weeks. Study 2 compared a dose ratio of 1:2 between rosuvastatin and simvastatin in lowering LDL-C with a 3.24% (95% CI 4.10 to 2.38) favor of rosuvastatin. Study 4 compared effects of atorvastatin 80 mg and rosuvastatin 20 mg in patients with ST elevation myocardial infarction in a 4-week therapy. Rosuvastatin 20 resulted in a 35% compared with atorvastatin 80 mg 34% (P=0.59) reduction in LDL-C levels. Study 1 demonstrated rosuvastatin to improve HDL-C levels in daily doses of 40 mg with statistical significance compared with atorvastatin, simvastatin and pravastatin. Study 1 demonstrated rosuvastatin to lower total cholesterol with statistical significance (P<0.002) across doses compared with atorvastatin, simvastatin and pravastatin. Study 1 also demonstrated rosuvastatin to lower triglycerides more. In daily doses of 40 mg rosuvastatin had a statistical significance (P<0.002) versus simvastatin and pravastatin, but not atorvastatin. The P value between rosuvastatin and atorvastatin was not mentioned, neither the P-value between atorvastatin, simvastatin and pravastatin.

    Conclusion: Statins are not equipotent. Rosuvastatin showed greater results in reducing LDL-C, triglycerides and total cholesterol with no increased risk of adverse events compared with atorvastatin, simvastatin and pravastatin. Rosuvastatin still lacks in clinical experience which makes needs for further studies on this topic.

  • 169.
    Demirel, Isak
    et al.
    Univ Örebro, Dept Clin Med, Sch Hlth & Med Sci, Örebro, Sweden.
    Säve, Susanne
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Kruse, Robert
    Univ Örebro, Dept Clin Med, Sch Hlth & Med Sci, Örebro, Sweden.
    Persson, Katarina
    Univ Örebro, Dept Clin Med, Sch Hlth & Med Sci, Örebro, Sweden.
    Expression of suppressor of cytokine signalling 3 (SOCS3) in human bladder epithelial cells infected with uropathogenic Escherichia coli2013In: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, Vol. 121, no 2, p. 158-167Article in journal (Refereed)
    Abstract [en]

    Suppressor of cytokine signalling (SOCS) proteins inhibit pro-inflammatory signalling mediated by Janus-activated kinase (JAK)-signal transducer and activator of transcription (STAT) pathways. To evade the immune response some pathogens appear to modify the host SOCS proteins. Uropathogenic Escherichia coli (UPEC) are able to subvert the host response evoked by bladder epithelial cells, but the mechanisms are not fully understood. The objective of this study was to investigate whether UPEC can modify the host SOCS and STAT3 response. Real time RT-PCR studies demonstrated an increased SOCS1 and SOCS3 expression in the isolated human bladder epithelial cell lines (RT-4 and 5637) in response to cytokines. UPEC strain IA2 increased SOCS3, but not SOCS1, mRNA levels with a peak at 6h after infection. The increase of SOCS3 was confirmed at the protein level by Western blotting. The UPEC strain IA2 caused a time-dependent decrease in the phosphorylation of STAT3. This study demonstrates that UPEC are able to affect SOCS3 and STAT3 signalling in human uroepithelial cells. The finding that UPEC are able to induce mediators involved in suppression of host cytokine signalling may help to elucidate how UPEC may circumvent the host response during urinary tract infection.

  • 170.
    Denk, Stephanie
    et al.
    Univ Hosp Ulm, Germany.
    Neher, Miriam D.
    Univ Hosp Ulm, Germany.
    Messerer, David A. C.
    Univ Hosp Ulm, Germany.
    Wiegner, Rebecca
    Univ Hosp Ulm, Germany.
    Nilsson, Bo
    Uppsala University.
    Rittirsch, Daniel
    Univ Hosp Zurich, Switzerland.
    Nilsson Ekdahl, Kristina
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Weckbach, Sebastian
    Ulm Univ, Germany.
    Ignatius, Anita
    Ulm Univ, Germany.
    Kalbitz, Miriam
    Univ Hosp Ulm, Germany.
    Gebhard, Florian
    Univ Hosp Ulm, Germany.
    Weiss, Manfred E.
    Univ Hosp Ulm, Germany.
    Vogt, Josef
    Ulm Univ, Germany.
    Radermacher, Peter
    Ulm Univ, Germany.
    Koehl, Joerg
    Univ Lubeck, Germany;Cincinnati Childrens Hosp Med Ctr, USA.
    Lambris, John D.
    Univ Penn, USA.
    Huber-Lang, Markus S.
    Univ Hosp Ulm, Germany.
    Complement C5a Functions as a Master Switch for the pH Balance in Neutrophils Exerting Fundamental Immunometabolic Effects2017In: Journal of Immunology, ISSN 0022-1767, E-ISSN 1550-6606, Vol. 198, no 12, p. 4846-4854Article in journal (Refereed)
    Abstract [en]

    During sepsis, excessive activation of the complement system with generation of the anaphylatoxin C5a results in profound disturbances in crucial neutrophil functions. Moreover, because neutrophil activity is highly dependent on intracellular pH (pH(i)), we propose a direct mechanistic link between complement activation and neutrophil pHi. In this article, we demonstrate that in vitro exposure of human neutrophils to C5a significantly increased pHi by selective activation of the sodium/hydrogen exchanger. Upstream signaling of C5a-mediated intracellular alkalinization was dependent on C5aR1, intracellular calcium, protein kinase C, and calmodulin, and downstream signaling regulated the release of antibacterial myeloperoxidase and lactoferrin. Notably, the pH shift caused by C5a increased the glucose uptake and activated glycolytic flux in neutrophils, resulting in a significant release of lactate. Furthermore, C5a induced acidification of the extracellular micromilieu. In experimental murine sepsis, pHi of blood neutrophils was analogously alkalinized, which could be normalized by C5aR1 inhibition. In the clinical setting of sepsis, neutrophils from patients with septic shock likewise exhibited a significantly increased pHi. These data suggest a novel role for the anaphylatoxin C5a as a master switch of the delicate pHi balance in neutrophils resulting in profound inflammatory and metabolic changes that contribute to hyperlactatemia during sepsis.

  • 171.
    Dhillon, Prakriti
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Cobalt-catalysed, regioselective C-H activation of amides with unsymmetrical 1,3-diynes using 8-aminoquinoline as a bidentate directing group2018Independent thesis Advanced level (degree of Master (Two Years)), 80 credits / 120 HE creditsStudent thesis
    Abstract [en]

    A cobalt-catalysed, ortho-directed, C-H activation of 8-aminoquinoline amides for the preparation of functionalised isoquinolones is reported. The C-H activation was performed with the amide derived from 8-aminoquinoline which acts as a bidentate directing group to facilitate the C-H activation at the ortho carbon atom of the amide towards annulation/cyclisation, with unsymmetrical 1,3-diynes. The work presented here is an exploration of the regiochemical outcome of an efficient and a novel route of synthesis that tries to gain a deeper insight into the regioselective preference for C-H activated annulations that result in the formation of a diverse range of alkynylated regioisomeric heterocycles. Of the four possible regioisomers, only one is formed as the major product depending on the stereoelectronic properties of the diyne in combination with the nature of the 8-aminoquinoline amide.

  • 172.
    Dragan, Smiljic
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Studies of small bicoid knock-down and overexpression at early and late stage of development in Drosophila melanogaster.2016Independent thesis Advanced level (degree of Master (One Year)), 20 credits / 30 HE creditsStudent thesis
  • 173.
    Drajem, Veronica
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Apotekskunders uppfattning om trygghet med sina läkemedel och behandling. Hur de erhållit information om dessa samt deras kunskap om EES.: - En enkätundersökning om det förekommer skillnader mellan olika åldersgrupper på apoteket2018Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    Abstract

    Pharmacists have for many years been an important part of health care. They have rescued many people from diseases and poisoning. It´s important that they ensure the right drug, dosage and administration in right time for each customer. Elderly people usually have more prescribes than younger which increases the risk of interactions.

    Poor compliance may result in increased morbidity or premature death. There are several reasons why treatment is not followed. Lack of information about the treatment of disease or information about the medications for both indication and side effects are some of them

    At all pharmacies in Sweden, EES, Electronic Expert Support, is available. The introduction of e-prescription in the 21st century has enabled an additional safety check for the pharmacist, using Electronic Expert Support (EES) for dispatching prescriptions. The current recipe is compared with other prescriptions where there are withdrawals and the prescriptions where there should be pharmaceuticals left to consume. If there is a risk of incorrect dose, double prescription, age warning, interactions, gender specific or if drug affecting disease, a signal is given at EES control showing strength and action that may, should be done.

    The purpose of the study was to investigate customers perception of advice at the pharmacy and if the use and knowledge of the EES (Elektroniskt Expertstöd) differed between different age groups. The survey was conducted using data collection from seven pharmacies located in five locations spread across Sweden. The collection was conducted for about 100 hours and generated in 277 participants. All participation was voluntary and anonymous. The participants were divided into three age groups: 40 years or younger, 41-60 and over 60 years. The collected data was analyzed by using IBM SPSS and a chi2 test was performed to see if there were any significant differences between the age-groups. The result was compiled and demonstrated in excel diagrams.

    There was no significant difference between the groups in terms of safety and information they received about their drugs. Most people received information about their medicines by the doctor, pharmacist or by reading the package leaflet. However, there was some difference regarding the use of the Internet in a search for information retrieval among those over 60 years. This may be due to lack of internet knowledge or physical impairment. There was also a significant difference when it came to the question of calling 1177 for information on medicines, where people 40 years or younger, called more often than other groups. This may be because they usually have younger children and may need advice regarding illness or injuries.

    There was a significant difference between the age-groups in consent to use EES were elderly people had consented more often. Elderly people usually have more drug prescribes than younger and therefore is it more useful for people over 60 years. The risk of interactions increases with the number of drugs.

  • 174.
    Duehrkop, Claudia
    et al.
    Uppsala University.
    Leneweit, Gero
    ABNOBA GmbH, Germany;Association for the Promotion of Cancer Therapy, Germany.
    Heyder, Christoph
    ABNOBA GmbH, Germany;Association for the Promotion of Cancer Therapy, Germany.
    Fromell, Karin
    Uppsala University.
    Edwards, Katarina
    Uppsala University.
    Nilsson Ekdahl, Kristina
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences. Uppsala University.
    Nilsson, Bo
    Uppsala University.
    Development and characterization of an innovative heparin coating to stabilize and protect liposomes against adverse immune reactions2016In: Colloids and Surfaces B: Biointerfaces, ISSN 0927-7765, E-ISSN 1873-4367, Vol. 141, p. 576-583Article in journal (Refereed)
    Abstract [en]

    Liposomes have been recognized as excellent drug delivery systems, but when they come in direct contact with different blood components they may trigger an immediate activation of the innate immune system. The aim of the present study was to produce long-circulating, blood-compatible liposomes by developing a construct of liposomes covered by a novel unique heparin complex (CHC; 70 heparin molecules per complex) to avoid recognition by the innate immune system. Unilamellar, cationic liposomes were produced by hand extrusion through a 100-nm polycarbonate membrane. Coating of liposomes with the macromolecular CHC was accomplished by electrostatic interactions. Dynamic light scattering as well as QCM-D measurements were used to verify the electrostatic deposition of the negatively charged CHC to cationic liposomes. The CHC-coated liposomes did not aggregate when in contact with lepirudin anti coagulated plasma. Unlike previous attempts to coat liposomes with heparin, this technique produced freely moveable heparin strands sticking out from the liposome surface, which exposed AT binding sites reflecting the anticoagulant potentials of the liposomes. In experiments using lepirudin-anticoagulated plasma, CHC-coated liposomes, in contrast to non-coated control liposomes, did not activate the complement system, as evidenced by low C3a and sC5b-9 generation and reduced leakage from the liposomes. In conclusion, we show that liposomes can be successfully coated with the biopolymer CHC, resulting in biocompatible and stable liposomes that have significant application potential. (C) 2016 Elsevier B.V. All rights reserved.

  • 175.
    Duong-Thi, Minh-Dao
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Introducing weak affinity chromatography to drug discovery with focus on fragment screening2013Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Fragment-based drug discovery is an emerging process that has gained popularity in recent years. The process starts from small molecules called fragments. One major step in fragment-based drug discovery is fragment screening, which is a strategy to screen libraries of small molecules to find hits. The strategy in theory is more efficient than traditional high-throughput screening that works with larger molecules. As fragments intrinsically possess weak affinity to a target, detection techniques of high sensitivity to affinity are required for fragment screening. Furthermore, the use of different screening methods is necessary to improve the likelihood of success in finding suitable fragments. Since no single method can work for all types of screening, there is a demand for new techniques. The aim of this thesis is to introduce weak affinity chromatography (WAC) as a novel technique for fragment screening.

    WAC is, as the name suggests, an affinity-based liquid chromatographic technique that separates compounds based on their different weak affinities to an immobilized target. The higher affinity a compound has towards the target, the longer it remains in the separation unit, and this will be expressed as a longer retention time. The affinity measure and ranking of affinity can be achieved by processing the obtained retention times of analyzed compounds.

    In this thesis, WAC is studied for fragment screening on two platforms. The first system comprised a 24-channel affinity cartridge that works in cooperation with an eight-needle autosampler and 24 parallel UV detector units. The second system was a standard analytical LC-MS platform that is connected to an affinity column, generally called WAC-MS or affinity LC-MS. The evaluation criteria in studying WAC for fragment screening using these platforms were throughput, affinity determination and ranking, specificity, operational platform characteristics and consumption of target protein and sample. The model target proteins were bovine serum albumin for the first platform, thrombin and trypsin for the latter. Screened fragments were either small molecule drugs, a thrombin-directed collection of compounds, or a general-purpose fragment library. To evaluate WAC for early stages of fragment elaboration, diastereomeric mixtures from a thrombin-directed synthesis project were screened.

    Although both analytical platforms can be used for fragment screening, WAC-MS shows more useful features due to easy access to the screening platform, higher throughput and ability to analyze mixtures. Affinity data from WAC are in good correlation with IC50 values from enzyme assay experiments. The possibility to distinguish specific from non- specific interactions plays an important role in the interpretation of WAC results. In this thesis, this was achieved by inhibiting the active site of the target protein to measure off-site interactions. WAC proves to be a sensitive, robust, moderate in cost and easy to access technique for fragment screening, and can also be useful in the early stages of fragment evolution.

    In conclusion, this thesis has demonstrated the proof of principle of using WAC as a new tool to monitor affinity and to select hits in fragment-based drug discovery. This thesis has indicated the primary possibilities, advantages as well as the limitations of WAC in fragment screening procedures.  In the future, WAC should be evaluated on other targets and fragment libraries in order to realize more fully the potential of the technology.

  • 176.
    Duong-Thi, Minh-Dao
    et al.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Bergström, Gunnar
    Linköping Univ, Sweden.
    Mandenius, Carl-Fredrik
    Linköping Univ, Sweden.
    Bergström, Maria
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Fex, Tomas
    Univ Gothenburg, Sweden.
    Ohlson, Sten
    Nanyang Technol Univ, Singapore.
    Comparison of weak affinity chromatography and surface plasmon resonance in determining affinity of small molecules2014In: Analytical Biochemistry, ISSN 0003-2697, E-ISSN 1096-0309, Vol. 461, p. 57-59Article in journal (Refereed)
    Abstract [en]

    In this study, we compared affinity data from surface plasmon resonance (SPR) and weak affinity chromatography (WAC), two established techniques for determination of weak affinity (mM-mu M) small molecule-protein interactions. In the current comparison, thrombin was used as target protein. In WAC the affinity constant (K-D) was determined from retention times, and in SPR it was determined by Langmuir isotherm fitting of steady-state responses. Results indicate a strong correlation between the two methods (R-2 = 0.995, P < 0.0001). (C) 2014 Elsevier Inc. All rights reserved.

  • 177.
    Duong-Thi, Minh-Dao
    et al.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences. Nanyang Technol University, Singapore.
    Bergström, Maria
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Edwards, Katarina
    Uppsala University.
    Eriksson, Jonny
    Uppsala University.
    Ohlson, Sten
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    To Yiu Ying, Janet
    Nanyang Technol University, Singapore.
    Torres, Jaume
    Nanyang Technol University, Singapore.
    Agmo Hernández, Víctor
    Uppsala University.
    Lipodisks integrated with weak affinity chromatography enable fragment screening of integral membrane proteins2016In: The Analyst, ISSN 0003-2654, E-ISSN 1364-5528, Vol. 141, no 3, p. 981-988Article in journal (Refereed)
    Abstract [en]

    Membrane proteins constitute the largest class of drug targets but they present many challenges in drug discovery. Importantly, the discovery of potential drug candidates is hampered by the limited availability of efficient methods for screening drug-protein interactions. In this work we present a novel strategy for rapid identification of molecules capable of binding to a selected membrane protein. An integral membrane protein (human aquaporin-1) was incorporated into planar lipid bilayer disks (lipodisks), which were subsequently covalently coupled to porous derivatized silica and packed into HPLC columns. The obtained affinity columns were used in a typical protocol for fragment screening by weak affinity chromatography (WAC), in which one hit was identified out of a 200 compound collection. The lipodisk-based strategy, which ensures a stable and native-like lipid environment for the protein, is expected to work also with other membrane proteins and screening procedures.

  • 178.
    Duong-Thi, Minh-Dao
    et al.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Bergström, Maria
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Fex, Tomas
    Astra& Zeneca R&D Mölndal, Mölndal, Sweden.
    Isaksson, Roland
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Ohlson, Sten
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    High-Throughput Fragment Screening by Affinity LC-MS2013In: Journal of Biomolecular Screening, ISSN 1087-0571, E-ISSN 1552-454X, Vol. 18, no 2, p. 160-171Article in journal (Refereed)
    Abstract [en]

    Fragment screening, an emerging approach for hit finding in drug discovery, has recently been proven effective by its first approved drug, vemurafenib, for cancer treatment. Techniques such as nuclear magnetic resonance, surface plasmon resonance, and isothemal titration calorimetry, with their own pros and cons, have been employed for screening fragment libraries. As an alternative approach, screening based on high-performance liquid chromatography separation has been developed. In this work, we present weak affinity LC/MS as a method to screen fragments under high-throughput conditions. Affinity-based capillary columns with immobilized thrombin were used to screen a collection of 590 compounds from a fragment library. The collection was divided into 11 mixtures (each containing 35 to 65 fragments) and screened by MS detection. The primary screening was performed in < 4 h (corresponding to > 3500 fragments per day). Thirty hits were defined, which subsequently entered a secondary screening using an active site-blocked thrombin column for confirmation of specificity. One hit showed selective binding to thrombin with an estimated dissociation constant (K-D) in the 0.1 mM range. This study shows that affinity LC/MS is characterized by high throughput, ease of operation, and low consumption of target and fragments, and therefore it promises to be a valuable method for fragment screening.

  • 179.
    Duong-Thi, Minh-Dao
    et al.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Bergström, Maria
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Fex, Tomas
    Astra&Zeneca R&D, Sweden.
    Svensson, Susanne
    Chalmers University of Technology, Sweden.
    Ohlson, Sten
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Isaksson, Roland
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Weak Affinity Chromatography for Evaluation of Stereoisomers in Early Drug Discovery2013In: Journal of Biomolecular Screening, ISSN 1087-0571, E-ISSN 1552-454X, Vol. 18, no 6, p. 748-755Article in journal (Refereed)
    Abstract [en]

    In early drug discovery (e.g. in fragment screening), recognition of stereoisomeric structures is valuable and guides medicinal chemists to focus only on useful configurations. In this work, we concurrently screened mixtures of stereoisomers and estimated their affinities to a protein target (thrombin) using weak affinity chromatography-mass spectrometry (WAC-MS). Affinity determinations by WAC showed that minor changes in stereoisomeric configuration could have major impact on affinity. The ability of WAC-MS to provide instant information about stereoselectivity and binding affinities directly from analyte mixtures is a great advantage in fragment library screening and drug lead development.

  • 180.
    Durmo, Daniela
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Generiskt utbyte på apotek: Enkätundersökning om apotekskunders generella uppfattning om generiskt utbyte med avseende på utbildningsnivå2018Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    Background: To reduce the increasing cost for pharmaceuticals on prescription in Sweden, the generic drug exchange was introduced in 2002. According to the law (2002:160) of drug benefits all pharmacies are forced to exchange the brand-name product/original for a generic drug, i.e. a drug that is covered by the Swedish drug benefit system and in addition has been found by The Swedish Medical Products Agency (MPA) to be equivalent to the brand-name product/original in question. The Dental and Pharmaceutical Benefits Agency, TLV, determines which available drug is the lowest price, "the product of the period". The reform has led to major economic savings for both the individual and the society. For some patients the generic drug exchange has resulted in increased safety problems in the form of medication errors, lack of drug effects, and new unwanted side effects. Insufficient information from prescribers and pharmacists and different names of drugs has led to confusion among patients. Purpose: The purpose of the study was to investigate the customers' experience of the generic drug exchange at pharmacies, the potential problems of generic exchange, and whether any differences in how the generic drug exchange is experienced can be explained by the customer's level of education. Method: The investigation was conducted as a survey, which consisted of 10 different multiple choice questions where the respondent was able to choose the answer best in line with their perception. Results and discussion: The majority (87%) of the participants stated that they had accepted the generic exchange. In general, there was no apparent difference in regards to the different levels of education. Nevertheless, among those with university/college as the highest level of education, there was a greater proportion of women (45%) than men (29%). A small percentage (22%) of the participants had experienced problems in connection with or after the exchange. Among the problems mentioned were, among other things, unknown name, tablet, or packaging; and new side effects. 42% of the participants had received information about the generic drug exchange from the medical doctors while 90% of the participants had received information at the pharmacy. No difference between different groups could be detected. The overall experience with the generic exchange showed that 81% of participants were satisfied with the exchange. No difference between different groups could be detected. Conclusion: The study showed that the main part of the (survey) participants has a positive attitude towards generic exchange. The majority of the participants felt that they had gotten adequate information regarding the exchange at the pharmacy (from the pharmacist), whilst the survey revealed that the medical doctors was insufficient in informing their patients about the possibility of generic exchange. There was no apparent difference amongst different groups when it comes to acceptance and general perception of the generic drug exchange.

  • 181.
    Eckerbert, My
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    CRISPR i cancerimmunologin: Kliniska prövningar, utmaningar och framtid2019Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    Understanding the biologi of tumors is an important prerequisite to develop new methods for cancer treatment. The gene editing tool Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) with CRISPR-associated proteins (Cas9), CRISPR-Cas9 is a new tool in cancer therapy, both for understanding the origins of the tumors and for finding treatments and drug targets. It is an adaptive immune system in prokaryotes. CRISPR is a programmable RNA- guided system which targets DNA. The technology is applicable in cancer immunology by e.g. manipulating T-cells. The purpose of this literature study was to: 1) investigate which cancer immunotherapy clinical trials, using CRISPR-Cas9, that are ongoing today and 2) which results have emerged so far; 3) how CRISPR-Cas9 can be delivered to cells in vivo; 4) which problems have arisen, and 5) what the future might hold for CRISPR within cancer research. The information was gathered from January to May 2019 from primarily PubMed, clinicaltrials.gov, and Google. Today, 8 clinical trials are ongoing but the studies have not yet published any results. One of the main challenges of CRISPR is finding a suitable methodology of delivery where viral methods is the one that has mainly been used. Many studies investigate possibility of lipid nanocarriers but as of today, no one single delivery system is superior to the others. The problems with CRISPR-Cas9 that have emerged is that it can cause cancer when editing cells that are missing p53 (an important tumor suppressing protein); it has pathogenic consequenses due to long deletions as Cas9 cuts DNA; and Cas9 can cut the DNA at off-targeted sites. In the future, CRISPR with different Cas-proteins, can be used to manufacture universal Chimeric antigen receptor T cells (CAR-T-cells), understanding the origin and development of tumors, finding new drug targets, deleting DNA-sequences from viruses that have incorporated their genome into ours, and maybe also for editing the germ line in order to reduce the risk of e.g. developing cancer.

  • 182.
    Eckered Göransson, Sara
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Kan probiotika lindra depression?2019Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    Previous research has shown a connection between our microbiota and physical health, and today a lot of research is also being done on whether it also can affect our mental health. Today, over four percent of the world's population suffers from depression, and this literature study has, by analysing seven studies and their results, attempted to answer the question of whether probiotics can alleviate depression. Either as primary treatment or as a supplement to other treatment. This literature study did not provide any definite answers to that question, other than that all the researchers involved in the studies analysed agree that more, longer and larger studies are needed before one can draw any conclusions.

  • 183.
    Edfors, Inger
    et al.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Johansson-Cederblad, Brita
    Linnaeus University, Faculty of Health and Life Sciences, Department of Biology and Environmental Science.
    Wikman, Susanne
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Linder, Cedric
    Uppsala universitet.
    Fokusgrupper avslöjar representationersmöjligheter och begränsningar för lärande i naturvetenskap2013Conference paper (Other academic)
  • 184.
    Edfors, Inger
    et al.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Wikman, Susanne
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Johansson-Cederblad, Brita
    Linnaeus University, Faculty of Health and Life Sciences, Department of Biology and Environmental Science.
    Linder, Cedric
    Uppsala University.
    University students' reflections on representations in genetics and stereochemistry revealed by a focus group approach2015In: NorDiNa: Nordic Studies in Science Education, ISSN 1504-4556, E-ISSN 1894-1257, Vol. 11, no 2, p. 169-179Article in journal (Refereed)
    Abstract [en]

    Genetics and organic chemistry are areas of science that students regard as difficult to learn. Part ofthis difficulty is derived from the disciplines having representations as part of their discourses. In orderto optimally support students’ meaning-making, teachers need to use representations to structure themeaning-making experience in thoughtful ways that consider the variation in students’ prior knowledge.Using a focus group setting, we explored 43 university students’ reasoning on representationsin introductory chemistry and genetics courses. Our analysis of eight focus group discussions revealedhow students can construct somewhat bewildered relations with disciplinary-specific representations.The students stated that they preferred familiar representations, but without asserting themeaning-making affordances of those representations. Also, the students were highly aware of the affordances of certain representations, but nonetheless chose not to use those representations in theirproblem solving. We suggest that an effective representation is one that, to some degree, is familiarto the students, but at the same time is challenging and not too closely related to “the usual one”.The focus group discussions led the students to become more aware of their own and others ways ofinterpreting different representations. Furthermore, feedback from the students’ focus group discussionsenhanced the teachers’ awareness of the students’ prior knowledge and limitations in students’representational literacy. Consequently, we posit that a focus group setting can be used in a universitycontext to promote both student meaning-making and teacher professional development in a fruitfulway.

  • 185.
    Edfors, Inger
    et al.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Wikman, Susanne
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Johansson-Cederblad, Brita
    Linnaeus University, Faculty of Health and Life Sciences, Department of Biology and Environmental Science.
    Linder, Cedric
    Uppsala Universitet.
    University students' reflections on representations in introductory genetics and stereochemistry2014Conference paper (Other academic)
    Abstract [en]

    Genetics and organic chemistry are areas of science that are regarded as difficult. Part of thisdifficulty is derived from them having representations as part of their disciplinary discourses. Inorder to optimally support students’ learning and meaning-making, teachers need to thoughtfullyuse representations to structure the learning experience in ways that open up the variation instudents’ prior knowledge. For our study, university students’ reasoning on representations ingenetics and organic chemistry was investigated using a focus group approach (8 groups, 4-8students/group). This revealed how students can construct somewhat bewildered relations withdisciplinary-specific representations. For instance, they stated that they preferred familiarrepresentations, but without asserting the meaning-making affordances of those representations.Also, the students were highly aware of the affordances in certain representations, but nonethelesschose not to use those representations in their problem solving. The focus group discussions ledthe students to become more aware of their own and others meaning-making. At the same time,feedback from the students’ focus group discussions enhanced the teacher’s awareness of thestudents’ prior knowledge and meaning-making. Consequently, we posit that a design focus groupmethodology can be fruitfully used both to promote teacher development and progression, andstudent learning.

  • 186.
    Ekedahl, Anders
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences. Medical Products Agency / Läkemedelsverket.
    Patients' "self-reconciliation" of the medication list compared with medication verification with pharmacist2013In: International Journal of Clinical Pharmacy, ISSN 2210-7703, Vol. 35, no 3, p. 505-505Article in journal (Other academic)
  • 187.
    Ekelund, Philip
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Effekt av Tracleer (bosentan) vid behandling av pulmonell arteriell hypertension2016Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [sv]

    Pulmonell arteriell hypertension är en sjukdom som engagerar de små arteriolerna och venolerna i lungkärlbädden. Det är främst arterioler som drabbas och det handlar om en ökad proliferation, remodellering samt minskad apoptos vilket leder till en hypertrof kärlvägg med minskat kärllumen. Det föreligger samtidigt en obalans av mediatorer som reglerar kärltonus. Tillsammans ökar förändringarna flödesmotståndet eller den pulmonella vaskulära resistensen och höger kammare försöker att kompensera för det ökade trycket samt upprätthålla normala hjärtminutvolymer. Det höga lungartärtrycket leder till ökat afterload, minskad slagvolym, högersidig hypertrofi av hjärtmuskelceller  och efterföljande högerkammarsvikt samt död. Tracleer (bosentan) är en endotelin-receptor antagonist och syftet med denna litteraturstudie var att utvärdera Tracleers effekt vid behandling av pulmonell arteriell hypertension. I studien granskades 6 artiklar hämtade från pubmed, 4 randomiserade kliniska prövningar och 2 långtidsstudier utan kontrollgrupp. Resultatet visar att Tracleer (bosentan) har klinisk effekt vid behandling av pulmonell arteriell hypertension, men det behövs flera studier för att helt kartlägga substansens effekt i samtliga undergrupper av sjukdomen. I två av fyra placebokontrollerade studier förbättrade patienter statistiskt signifikant sina funktionella klassificeringar. I tre av studierna förbättrade patienterna sitt resultat i ett 6 minuters gångtest statistiskt signifikant. Sammanfattningsvis är Tracleer (bosentan) ett bra alternativ för behandling av pulmonell arteriell hypertension, men nya behandlingsalternativ behövs och kombinationsterapi av flera preparatgrupper bör övervägas om patienterna är svårt sjuka eller befinner sig i funktionell klass IV som Tracleer (bosentan) inte är indicerat för. I framtida forskning skulle adekvata långtidsstudier och kombinationsterapi vara intressanta områden att utvärdera. 

  • 188.
    Ekman, Anna
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Får för få FaR?: FaR i teori och praktik2019Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    Physical activity promotes health, although many individuals are not active enough. The Swedish method Physical acticity on prescription (FaR) is used in the health care sector to help patients achieve a better health through physical activity.

    This bachelor’s thesis aims to estimate how many primary care patients that meet the criteria to be eligible for a FaR prescription and, through a literature study, investigate how health care prescribers adhere to the FaR method and which factors affect their prescribing a FaR.

    The concept of FaR is in theory well defined, and the estimate indicate that there is a large number of primary care patients who would benefit from a FaR prescription, such as it is defined.

    In practice, however, the concept is not as clearly defined. The literature study indicates varying adherence to the different method components and suggests several factors affecting whether FaR is prescribed or not. This makes it difficult to quantify the usefulness of increasing the number of FaR prescriptions.

  • 189.
    Ekstedt, Sandra
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences. Karolinska institutet.
    Effect of IL-13 on Serotonin mediated Airway Smooth Muscle Contraction2013Independent thesis Advanced level (degree of Master (One Year)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    Introduction: Asthma is a disease that occurs worldwide and approximately 300 million people carry this disease. It is characterized by chronic inflammation, airway obstruction and airway hyper-responsiveness (AHR). This T-lymphocyte controlled disease has symptoms such as coughing, wheezing, and chest tightness. In addition to chronic inflammation, asthma is also caused by overproduction of mucus and airway wall remodelling. The chronic inflammation and airway wall remodelling are suggested to contribute to the AHR and airway obstruction. AHR is a way to measure the reactivity in the airways in asthmatics. IL-13 has been shown to play an important role in the development of AHR, and biopsies from bronchial submucosa and air way smooth muscle (ASM) in humans have shown an increased concentration of IL-13 in severe asthma.

    Aim: The aim of this work was to evaluate if IL-13 is able to enhance the 5-HT response in mouse tracheal segments, which had been cultured for 2 days and, if so, try to unravel the underlying mechanism for this phenomenon. Literature reports that IL-13 enhanced contractions in mouse trachea in presence of KCl and CCH. Earlier work within this project did not find any clear proof for this observation. However, in this work this observation will be evaluated in a more controlled fashion by correcting for size and location of the trachea.

    Methods: The trachea was removed from Balp/c mice and cultured in small wells for two days in DMEM medium and various additions were performed to the medium for understanding the effect of e.g. IL-13 on the cells. The contractility change due to IL-13 and various additions in segments challenged with KCL, CCH and 5-HT were measured in a tissue-organ bath.

    Results and Conclusion: A more enhanced CCH induced contraction of IL-13 treated segments was obtained for the lower part compared to the upper part of the trachea. IL-13 enhanced the response in the ASM to 5-HT after two days of culturing. An increased concentration of the cytokine IL-13 in the airways from TH2-cells enhances the reactivity to 5-HT in the ASM. The underlying mechanism might involve JNK and ERK but more experiments are needed to statistically ensure this claim.

  • 190.
    Ekstrand-Hammarström, Barbro
    et al.
    Swedish Def Res Agcy, Linköping.
    Hong, Jaan
    Uppsala University.
    Davoodpour, Padideh
    Uppsala University.
    Sandholm, Kerstin
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Nilsson Ekdahl, Kristina
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences. Uppsala University.
    Bucht, Anders
    Umeå University.
    Nilsson, Bo
    Uppsala University.
    TiO2 nanoparticles tested in a novel screening whole human blood model of toxicity trigger adverse activation of the kallikrein system at low concentrations2015In: Biomaterials, ISSN 0142-9612, E-ISSN 1878-5905, Vol. 51, p. 58-68Article in journal (Refereed)
    Abstract [en]

    There is a compelling need to understand and assess the toxicity of industrially produced nanoparticles (NPs). In order to appreciate the long-term effects of NPs, sensitive human-based screening tests that comprehensively map the NP properties are needed to detect possible toxic mechanisms. Animal models can only be used in a limited number of test applications and are subject to ethical concerns, and the interpretation of experiments in animals is also distorted by the species differences. Here, we present a novel easy-to-perform highly sensitive whole-blood model using fresh non-anticoagulated human blood, which most justly reflects complex biological cross talks in a human system. As a demonstrator of the tests versatility, we evaluated the toxicity of TiO2 NPs that are widely used in various applications and otherwise considered to have relatively low toxic properties. We show that TiO2 NPs at very low concentrations (50 ng/mL) induce strong activation of the contact system, which in this model elicits thromboinflammation. These data are in line with the finding of components of the contact system in the protein corona of the TiO2 NPs after exposure to blood. The contact system activation may lead to both thrombotic reactions and generation of bradykinin, thereby representing fuel for chronic inflammation in vivo and potentially long-term risk of autoimmunity, arteriosclerosis and cancer. These results support the notion that this novel whole-blood model represents an important contribution to testing of NP toxicity. (C) 2015 Elsevier Ltd. All rights reserved.

  • 191.
    Ekström, Agneta
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Kunskap om smitta, smittspridning och basala hygienrutiner hos personal inom vården2015Independent thesis Advanced level (degree of Master (One Year)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    The use of basic routines for hygiene in healthcare is essential to reduce the risk of spreading healthcare associated infections. The purpose of this study was to investigate the knowledge regarding infections and the transmission of infections and the knowledge of basic routines for hygiene. A quantitative descriptive study was conducted consisting of a questionary that was handed out during a day to healthcare workers in surgical and medical wards at Västmanland Hospital in Västerås. A total of 131 persons participated in the study. The results showed that the participants had a good education in the subjects of microbiology and infection control. The participants also reported that they at one or several occasions had received information regarding basic routines for hygiene. The result from the survey showed that the knowledge in these subjects was good among the respondents. However, only few of the respondents could correctly reiterate the content of the basic routines for hygiene. The other respondents were not completely sure about the content. Despite the good knowledge among the respondents there is always a risk of carelessness with routines for basic hygiene. Therefore, it is important to constantly work on the follow-up of routines for basic hygiene and education regarding infection transmission in health care.

  • 192.
    Ekström, Sara
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Buller som stressor i skolmatsalar: En fördjupning av Barnmiljöhälsorapport 2013 i samarbete med Landstinget i Jönköpings län2014Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    Background: The child health report of 2013 was undertaken in the district of Jönköping, Sweden. The results of this survey indicated that the 12 year olds that participated in the study were bothered by the noise in the dining area of their school. An elevated level of noise can affect the human body in a negative way, and can lead to an increased level of stress. Exposure to elevated levels of noise gives enhanced excretion of corticotrophin releasing hormone (CRH). CRH is a hormone that can have a negative impact on the normal function of the gastrointestinal tract. Elevated noise will affect the health of people being exposed, and entails a health hazard.

    Aim: The aim of this study was to evaluate the relationship between the noise in school dining areas and the self reflected health of 858 12 year old students from the district of Jönköping, Sweden.

    Method: The analysis was based on a child health survey 2011; evaluating the student´s reflection of the exposure of noise in relation to their own estimated health status.

    Results: The results from the child health survey 2011 did show that the students being most affected by noise also experienced a lower self reflected health compared to the students less affected by noise in the school dining area. 

    Conclusion: The findings of this study indicate that students experience an overall lower level of health if they feel negatively affected by noise. To be able to improve child health, further research needs to be undertaken regarding this issue. The effects of stress hormones need to be investigated further, as well as the relationship between excretions of stress hormones in the body and the level of surrounding noise.

  • 193.
    El Saleh, Iman
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    En jämförelse av effekten hos protonpumpshämmare och histamin-2-receptorantagonister vid behandling av NSAID-associerade magsår2019Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    Non-steroidal anti-inflammatory drug (NSAID) is a collective name for various antipyretic, analgesic and anti-inflammatory drugs and are among the most used drugs in the world. However, the use of NSAIDs can lead to gastric ulcers. In this literature study, the effects of PPI and H2RA, respectively, in the treatment and prevention of NSAID-induced gastric ulcer are studied. Five clinical studies were selected using the PubMed database. The reported results were carefully analyzed and compiled. The results in the different studies indicate that PPI is 5 to 15% more effective than H2RA in terms of efficacy in the treatment of NSAID-induced gastric ulcer and that PPI is 10% more effective than H2RA in terms of efficacy in the prevention of NSAID-induced gastric ulcer.

  • 194.
    Elias, Ali
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Vankomycins effektivitet i jämförelse med andra läkemedel mot meticillinresistent Staphylococcus aureus2017Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [sv]

    Staphylococcus aureus (S. aureus) är en av många bakterier som har utvecklat resistens mot olika typer av antibiotika. På mitten av 1940-talet detekterades penicillinresistent S. aureus. Meticillinresistent S. aureus (MRSA) identifierades sedan år 1961. Vankomycin, en tricyklisk hydrofil glykopeptid, används fortfarande som ett förstahandsläkemedel mot allvarliga MRSA-infektioner trots förekomsten av vankomycinresistens och tillgången till nya MRSA-läkemedel. Syftet med detta arbete är att jämföra effektiviteten av vankomycin med andra läkemedel vid behandlingen av MRSA. Detta görs för att kunna bedöma om användningen av vankomycin som ett förstahandsläkemedel mot MRSA bör omprövas. Detta arbete är en litteraturstudie som är gjord med hjälp av artiklar från databasen PubMed. Det hittades fem studier om behandlingen av olika MRSA-infektioner. Linezolid visade sig vara effektivare än vankomycin vid behandlingen av hud- och mjukdelsinfektioner samt nosokomial pneumoni. Daptomycin var inte underlägset vankomycin mot bakteriemi och endokardit. Arbekacin visade sig vara mindre effektiv än vankomycin mot kronisk mediaotit. Kombinationen trimetoprim/ sulfametoxazol (TMP/SMX) verkade vara överlägset vankomycin vid behandlingen av hälsovårdsförvärvad pneumoni och ventilatorförvärvad pneumoni. Den slutsats som kan dras i detta arbete är att vid en jämförelse av vankomycin med linezolid, daptomycin, TMP/SMX och arbekacin vid behandling av olika MRSA-infektioner var vankomycin överlag mindre effektiv. Det kan därför vara lämpligt att ompröva ifall vankomycin bör användas som ett förstahandsläkemedel mot MRSA.

  • 195.
    Elias, Mohammed
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Verifiering och analys av anti-dsDNA antikroppar med instrumentet Phadia 2502017Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [sv]

    Autoantikroppar är antikroppar som attackerar en individs egen vävnad. Riktas dessa mot antigener från cellkärnan kallas de för ANA. Exempel på dessa är anti-dsDNA antikroppar som associeras med sjukdomen SLE. Med hjälp av metoderna ELISA, CLIFT eller FARR-radioimmunoassay kan anti-dsDNA antikroppar analyseras och tillsammans med kliniska symptom såsom ansiktserytem kan diagnosen SLE ställas. Syftet med examensarbetet var att undersöka analys av anti-dsDNA antikroppar med hjälp av instrumentet Phadia 250 vars princip är en automatiserad ELISA, för att se om det kan användas som screeningmetod istället för CLIFT. 20 EQUALIS-serumprover (externa kontrollprover) analyserades med Phadia 250 och de Phadia 250-positiva proverna analyserades ytterligare en gång med CLIFT. Därefter analyserades 44 patienters serumprover (21 positiva och 23 negativa, tidigare analyserade med CLIFT) med Phadia 250. Patientprovernas resultat gav 70 % sensitivitet och 86 % specificitet med Phadia 250. Phadia 250-resultat som ej överensstämde med förväntade resultat på EQUALIS- och patientproverna erhölls i flera fall. Vid en noggrannare granskning av EQUALIS-proverna noterades att liknande resultat erhållits av andra laboratorier som använt likartade metoder. EQUALIS-proverna var initialt analyserade och kategoriserade enligt CLIFT, vilket innebar att hög överensstämmelse kunde förväntas med den egna CLIFT-metoden. Slutsatsen av studien är att underlaget för att införa metoden i rutindiagnostiken är inte tillräckligt utifrån de erhållna resultaten. Det krävs ytterligare studier samt granskning av inkluderade patienters journaler för att säkrare bedöma metodernas korrelation till sjukdomen.

  • 196.
    Elmlund, Louise
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Cell-Antibody Interactions Studied Using HerceptinTM (trastuzumab) binding to SKOV-3 epithelial cancer cells characterized by Attana™ Quartz Crystal Microbalance Technology2013Conference paper (Other academic)
  • 197.
    Elmlund, Louise
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    QCM-based sensing using biological and biomimetic interfaces2014Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The objective of this thesis was to explore novel approaches for studying molecular recognition at biological and biomimetic surfaces using the quartz crystal microbalance (QCM) biosensor technique. The first two papers focused on the synthesis and study of biotin selective polymer films prepared using the molecularly imprinted polymer (MIP) technique. Control over polymer structure is of importance for sensor reproducibility and sensitivity, and was addressed in Paper I where a simple strategy for fabricating uniform thin biotin imprinted polymer films was employed. In Paper II the binding of biotin moieties to thin (3-5 nm) biomimetic polymer films was examined and consequences for sensor performance discussed. The potential for using QCM as a tool for assessing the binding of small peptides derived from phage display screening was presented Paper III. Here, screening of a phage peptide library against immobilized adenine resulted in candidate peptides that were studied using this technique. In Paper IV a whole cell-based biosensor was developed for studying interactions with cell membrane-incorporated targets. Epithelial cancer cells, SKOV3, were attached to QCM sensor chips and the binding of the monoclonal antibody HerceptinTM was studied. This approach demonstrates the potential of using QCM to study binding to membrane-incorporated targets, an alternative to assays based upon immobilized receptor structures lacking their natural context.

  • 198.
    Elmlund, Louise
    et al.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Käck, Camilla
    Attana AB.
    Aastrup, Teodor
    Attana AB.
    Nicholls, Ian A.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences. Uppsala University.
    Study of the Interaction of Trastuzumab and SKOV3 Epithelial Cancer Cells Using a Quartz Crystal Microbalance Sensor2015In: Sensors, ISSN 1424-8220, E-ISSN 1424-8220, Vol. 15, no 3, p. 5884-5894Article in journal (Refereed)
    Abstract [en]

    Analytical methods founded upon whole cell-based assays are of importance in early stage drug development and in fundamental studies of biomolecular recognition. Here we have studied the binding of the monoclonal antibody trastuzumab to human epidermal growth factor receptor 2 (HER2) on human ovary adenocarcinoma epithelial cancer cells (SKOV3) using quartz crystal microbalance (QCM) technology. An optimized procedure for immobilizing the cells on the chip surface was established with respect to fixation procedure and seeding density. Trastuzumab binding to the cell decorated sensor surface was studied, revealing a mean dissociation constant, K-D, value of 7 +/- 1 nM (standard error of the mean). This study provides a new perspective on the affinity of the antibody-receptor complex presented a more natural context compared to purified receptors. These results demonstrate the potential for using whole cell-based QCM assay in drug development, the screening of HER2 selective antibody-based drug candidates, and for the study of biomolecular recognition. This real time, label free approach for studying interactions with target receptors present in their natural environment afforded sensitive and detailed kinetic information about the binding of the analyte to the target.

  • 199.
    Elmlund, Louise
    et al.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Suriyanarayanan, Subramanian
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Wiklander, Jesper G.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Aastrup, Teodor
    Attana AB, Stockholm.
    Nicholls, Ian A.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences. Uppsala University.
    Biotin selective polymer nano-films2014In: Journal of Nanobiotechnology, ISSN 1477-3155, E-ISSN 1477-3155, Vol. 12, article id 8Article in journal (Refereed)
    Abstract [en]

    Background: The interaction between biotin and avidin is utilized in a wide range of assay and diagnostic systems. A robust material capable of binding biotin should offer scope in the development of reusable assay materials and biosensor recognition elements. Results: Biotin-selective thin (3-5 nm) films have been fabricated on hexadecanethiol self assembled monolayer (SAM) coated Au/quartz resonators. The films were prepared based upon a molecular imprinting strategy where N, N'-methylenebisacrylamide and 2-acrylamido-2-methylpropanesulfonic acid were copolymerized and grafted to the SAM-coated surface in the presence of biotin methyl ester using photoinitiation with physisorbed benzophenone. The biotinyl moiety selectivity of the resonators efficiently differentiated biotinylated peptidic or carbohydrate structures from their native counterparts. Conclusions: Molecularly imprinted ultra thin films can be used for the selective recognition of biotinylated structures in a quartz crystal microbalance sensing platform. These films are stable for periods of at least a month. This strategy should prove of interest for use in other sensing and assay systems.

  • 200.
    Elmlund, Louise
    et al.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Suriyanarayanan, Subramanian
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Wiklander, Jesper
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Nicholls, Ian A.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences. Uppsala University.
    Simple Strategy for Steering Polymer Film Formation on QCM Sensor SurfacesManuscript (preprint) (Other academic)
1234567 151 - 200 of 894
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