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  • 251.
    Friedman, Ran
    et al.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Boye, Kjetil
    Flatmark, Kjersti
    Molecular modelling and simulations in cancer research2013In: Biochimica et Biophysica Acta. CR. Reviews on Cancer, ISSN 0304-419X, E-ISSN 1879-2561, Vol. 1836, no 1, p. 1-14Article, review/survey (Refereed)
    Abstract [en]

    The complexity of cancer and the vast amount of experimental data available have made computer-aided approaches necessary. Biomolecular modelling techniques are becoming increasingly easier to use, whereas hardware and software are becoming better and cheaper. Cross-talk between theoretical and experimental scientists dealing with cancer-research from a molecular approach, however, is still uncommon. This is in contrast to other fields, such as amyloid-related diseases, where molecular modelling studies are widely acknowledged. The aim of this review paper is therefore to expose some of the more common approaches in molecular modelling to cancer scientists in simple terms, illustrating success stories while also revealing the limitations of computational studies at the molecular level.

  • 252.
    Friedman, Ran
    et al.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences. University of Zürich, Switzerland.
    Caflisch, Amedeo
    University of Zürich, Switzerland.
    Wild type and mutants of the HET-s(218-289) prion show different flexibility at fibrillar ends: A simulation study2014In: Proteins: Structure, Function, and Bioinformatics, ISSN 0887-3585, E-ISSN 1097-0134, Vol. 82, no 3, p. 399-404Article in journal (Refereed)
    Abstract [en]

    The C-terminal segment (residues 218–289) of the HET-s protein of the filamentous fungus Podosporina anserina is a prion-forming domain. The structural model of the HET-s(218–289) amyloid fibril based on solid-state nuclear magnetic resonance (NMR) restraints shows a β solenoid topology which is comprised of a β-sheet core and interconnecting loops. For the single-point mutants Phe286Ala and Trp287Ala, slower aggregation rates in vitro and loss of prionic infectivity have been reported recently. Here we have used molecular dynamics to compare the flexibility of the mutants and wild type. The simulations, initiated from a trimeric aggregate extracted from the NMR structural model, show structural stability on a 100-ns time scale for wild type and mutants. Analysis of the fluctuations along the simulations reveals that the mutants are less flexible than the wild type in the C-terminal segment at only one of the two external monomers. Analysis of interaction energy and buried accessible surface indicates that residue Phe286 in particular is stabilized in the Trp287Ala mutant. The simulation results provide an atomistic explanation of the suggestion (based on indirect experimental evidence) that flexibility at the protofibril end(s) is required for fibril elongation. Moreover, they provide further evidence that the growth of the HET-s amyloid fibril is directional.

  • 253.
    Friedman, Ran
    et al.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Khalid, Syma
    Univ Southampton, UK.
    Aponte-Santamaria, Camilo
    Univ Los Andes, Colombia;Heidelberg Univ, Germany.
    Arutyunova, Elena
    Univ Alberta, Canada.
    Becker, Marlon
    Univ Munster, Germany.
    Boyd, Kevin J.
    Univ Connecticut, USA.
    Christensen, Mikkel
    Aarhus Univ, Denmark;Sinodanish Ctr Educ & Res, Peoples Republic of China.
    Coimbra, Joao T. S.
    Univ Porto, Portugal.
    Concilio, Simona
    Univ Salerno, Italy.
    Daday, Csaba
    Heidelberg Inst Theoret Studies, Germany.
    van Eerden, Floris J.
    Univ Groningen, Netherlands.
    Fernandes, Pedro A.
    Univ Porto, Portugal.
    Graeter, Frauke
    Heidelberg Univ, Germany;Heidelberg Inst Theoret Studies, Germany.
    Hakobyan, Davit
    Univ Munster, Germany.
    Heuer, Andreas
    Univ Munster, Germany.
    Karathanou, Konstantina
    Free Univ Berlin, Germany.
    Keller, Fabian
    Univ Munster, Germany.
    Lemieux, M. Joanne
    Univ Alberta, Canada.
    Marrink, Siewert J.
    Univ Groningen, Netherlands.
    May, Eric R.
    Univ Connecticut, USA.
    Mazumdar, Antara
    Univ Groningen, Netherlands.
    Naftalin, Richard
    Kings Coll London, UK.
    Pickholz, Monica
    Univ Buenos Aires, Argentina.
    Piotto, Stefano
    Univ Salerno, Italy.
    Pohl, Peter
    Johannes Kepler Univ Linz, Austria.
    Quinn, Peter
    Kings Coll London, UK.
    Ramos, Maria J.
    Univ Porto, Portugal.
    Schiott, Birgit
    Aarhus Univ, Denmark.
    Sengupta, Durba
    Natl Chem Lab, India.
    Sessa, Lucia
    Univ Salerno, Italy.
    Vanni, Stefano
    Univ Fribourg, Switzerland.
    Zeppelin, Talia
    Aarhus Univ, Denmark.
    Zoni, Valeria
    Univ Fribourg, Switzerland.
    Bondar, Ana-Nicoleta
    Free Univ Berlin, Germany.
    Domene, Carmen
    Univ Bath, UK;Univ Oxford, UK.
    Understanding Conformational Dynamics of Complex Lipid Mixtures Relevant to Biology2018In: Journal of Membrane Biology, ISSN 0022-2631, E-ISSN 1432-1424, Vol. 251, no 5-6, p. 609-631Article, review/survey (Refereed)
    Abstract [en]

    This is a perspective article entitled "Frontiers in computational biophysics: understanding conformational dynamics of complex lipid mixtures relevant to biology" which is following a CECAM meeting with the same name.

  • 254.
    Friman, Janina
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Insulära loben - spindeln i nätet vid anorexia nervosa: En litteraturstudie med fokus på individer tillfrisknade från anorexia nervosa2018Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    Background: Different factors co-operate in the development of anorexia nervosa and contribute to the complexity of the disease. Anorexia nervosa is characterized by a lack of insight about being ill and a low weight that is maintained with a desire to be thin. Recovery from anorexia nervosa is a difficult process. Many recovered individuals report that they still have problematic thoughts about food and problems with their body image. With that in mind there is an interest for the question if full recovery is possible. That means a recovery when the person feels recovered not just don´t meet the requirement for anorexia nervosa any longer. The question is supported by the fact that individuals currently ill in anorexia nervosa shows different activation patterns in the brain. The insula is a part of the brain that integrates different processes and contributes to the body image. Individuals currently ill in anorexia nervosa shows different activation patterns in the insula

    Aim of the study: This study aim to study activation patterns in the insula when different stimulus is presented for recovered individuals. The study aim to get closer to an answer if there is premorbid traits in the insula that predispose for the development of anorexia nervosa.

    Methods: Literature review. Selected cross-sectional studies are reviewed further where a group of recovered individuals is compared to a group of people that never been diagnosed with anorexia nervosa.

    Results: Greater activation of the anterior insula is notable during an anticipation phase when the individual anticipate pictures of food (p<0.001). Anticipation of painful stimuli also shows greater activation of the anterior insula in recovered individuals (t-value 3.46). The subjective ratings of how enjoyable the anticipation phase was didn´t correlate with the measurements of the activation pattern i the insula. The posterior insula showed lower activation during pain stimulation in the recovered group (t-value 5.10). The anterior insula showed lower response to the taste of sucrose in the recovered group. No statistic significant group differences were found when artificial sweeteners were present. Prediction error resulted in a greater activation in anterior insula in the recovered group (p<0.05). Higher structural white matter connectivity between insula, orbitofrontal cortex and striatum but less fiber integrity in the recovered group (p<0.007).

    Discussion: This study found different activation patterns in individuals recovered from anorexia nervosa. The anticipation phase creates more anxiety in the recovered group and the anterior insula shows greater activation.

    The mismatch between the subjective experience and the activation pattern in the insula suggest altered integration that might be a premorbid trait.

    The lack of BMI correlations between fiber structural connectivity and integrity supports the hypothesis about premorbid traits in insula.

    Conclusion: This study is unable to determine an answer to the question if there are premorbid traits in the insula. The results of this study propose that different activation patterns in the insula may predispose for the development of anorexia nervosa. The results contribute with a better understanding of the complexity of anorexia nervosa and why there is a huge relapse rate. fMRI before the individual develop anorexia nervosa could clarify the results.

  • 255.
    Fromell, Karin
    et al.
    Uppsala University.
    Duhrkop, Claudia
    Uppsala University.
    Johansson, Ulrika
    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.
    Nilsson, Bo
    Uppsala University.
    Forms of contact-activated C3 associated with AP convertase formation2017In: Molecular Immunology, ISSN 0161-5890, E-ISSN 1872-9142, Vol. 89, p. 141-141Article in journal (Other academic)
  • 256.
    Fromell, Karin
    et al.
    Uppsala Universit.
    Duhrkop, Claudia
    Uppsala University.
    Kozarcanin, Huda
    Uppsala University.
    Johansson, Ulrika
    Uppsala University.
    Skjoedt, Mikkel-Ole
    Rigshosp, Denmark.
    Garred, Peter
    Rigshosp, Denmark.
    Nilsson Ekdahl, Kristina
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences. Uppsala University.
    Nilsson, Bo
    Uppsala University.
    The lectin pathway of complement and the contact/kallikrein system are integrated2018In: Molecular Immunology, ISSN 0161-5890, E-ISSN 1872-9142, Vol. 102, p. 151-152Article in journal (Other academic)
  • 257.
    Fromell, Karin
    et al.
    Uppsala University.
    Johansson, Ulrika
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences. Uppsala University.
    Duhrkop, Claudia
    Uppsala University.
    Adler, Anna
    Uppsala University.
    Usterud, Emma
    Uppsala University.
    Hamad, Osama A.
    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.
    Generation of an alternative pathway convertase by contact-activated C3 is dependent on the conformation of C32018In: Molecular Immunology, ISSN 0161-5890, E-ISSN 1872-9142, Vol. 102, p. 193-193Article in journal (Other academic)
  • 258.
    Fromell, Karin
    et al.
    Uppsala University.
    Yang, Yi
    University of Gothenburg.
    Nilsson Ekdahl, Kristina
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences. Uppsala University.
    Nilsson, Bo
    Uppsala University.
    Berglin, Mattias
    Gothenburg University;RISE Res Inst Sweden Chem Mat & Surfaces.
    Elwing, Hans
    University of Gothenburg.
    Absence of conformational change in complement factor 3 and factor XII adsorbed to acrylate polymers is related to a high degree of polymer backbone flexibility2017In: Biointerphases, ISSN 1934-8630, E-ISSN 1559-4106, Vol. 12, no 2, article id 02D417Article in journal (Refereed)
    Abstract [en]

    In previous investigations, the authors have examined the adsorption of albumin, immunoglobulin, and fibrinogen to a series of acrylate polymers with different backbone and side-group flexibility. The authors showed that protein adsorption to acrylates with high flexibility, such as poly(lauryl methacrylate) (PLMA), tends to preserve native conformation. In the present study, the authors have continued this work by examining the conformational changes that occur during the binding of complement factor 3 (C3) and coagulation factor XII (FXII). Native C3 adsorbed readily to all solid surfaces tested, including a series of acrylate surfaces of varying backbone flexibility. However, a monoclonal antibody recognizing a "hidden" epitope of C3 (only exposed during C3 activation or denaturation) bound to the C3 on the rigid acrylate surfaces or on polystyrene (also rigid), but not to C3 on the flexible PLMA, indicating that varying degrees of conformational change had occurred with binding to different surfaces. Similarly, FXII was activated only on the rigid poly(butyl methacrylate) surface, as assessed by the formation of FXIIa-antithrombin (AT) complexes; in contrast, it remained in its native form on the flexible PLMA surface. The authors also found that water wettability hysteresis, defined as the difference between the advancing and receding contact angles, was highest for the PLMA surface, indicating that a dynamic change in the interface polymer structure may help protect the adsorbed protein from conformational changes and denaturation. (C) 2017 Author(s).

  • 259.
    Fältskog, Emma
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Effekter av fysisk aktivitet på depression hos vuxna: En litteraturstudie2018Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [sv]

    Bakgrund: Depression är en av våra största folksjukdomar idag och har i genomsnitt sitt utbrott i 20 års åldern. Läkemedel och terapi är den behandling som traditionellt används idag, men även fysisk aktivitet till viss del för behandling av lättare form av depression.

    Syfte: Syftet med studien är att undersöka vad fysisk aktivitet har för effekter på depression hos vuxna.

    Metod: Femton originalartiklar som undersökte vilken effekt fysisk aktivitet har på depression analyserades och sammanfattades i denna litteraturstudie. Studierna som inkluderades undersöker vuxna personer som lider av depression utan andra bakomliggande sjukdomar.

    Resultat: Resultatet visar på positiva effekter av fysisk aktivitet på depressiva symptom. Åtta (53%) studier påvisar statistisk signifikans medan sju (47%) stycken inte kan påvisa någon signifikans mellan enbart traditionell behandling, behandling med fysisk aktivitet som tillägg till traditionell behandling eller mellan olika intensitet och duration av fysisk aktivitet.

    Slutsats: Alla studier visar på att fysisk aktivitet minskar symptom av depression hos vuxna. Dock är inte alla resultat statistisk signifikanta och det råder stor oenighet hos forskarna.

  • 260.
    Gacic, Natasha
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Metodjämförelse mellan instrumenten Vitros 5,1 FS och QuikRead CRP för analysen P-CRP2013Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    In studies of serum, in the early 1930s, from patients with pneumonia, a factor was found. It could agglutinate certain pneumococcal species. This factor, which later became known as C-reactive protein (CRP), increased sharply during the early and middle stages of the disease. CRP was identified as an acute phase protein and found especially in bacterial infections. CRP is synthesized in the liver by stimulation of interleukin 6 (IL-6), which is produced by the monocytes, and consists of five non-covalently bound subunits.

    The aim of this study was to compare two different analytical instruments (Vitros 5.1 FS Ortho-Clinical Diagnostics and QuikRead CRP Orion Diagnostica) for CRP analysis. In this study, Vitros 5.1 FS is used as a reference instrument. QuikRead CRP is a small instrument intended for patient-near testing.

    Vitros 5.1 FS (Ortho-Clinical Diagnostics a Johmon-Johmon Company, Rochester, NY, U.S.A) is a fully automated instrument for measuring various analytes of clinical importance in body fluids. For analysis of CRP, plasma is used. The amount of CRP is obtained by measuring turbidity at a specific wavelength in an Immuno-turbidimetric reaction. QuikRead CRP (Orion Diagnostica, Espoo, Finland) is an immuno-turbidimetric test in which micro-particles coated with anti-human CRP are used to measure the amount of CRP in whole blood, plasma or serum.

    Comparison between Vitros 5.1 FS and QuikRead CRP for the P-CRP analysis shows a good correlation (R= 0.997) of the mean value from the analysis I, II and III.  An intercept of -8.52 shows a decrease in the values of CRP for QuikRead comparatively Vitros 5.1 FS.  Bland-Altman-plot shows a slightly increased spread of results. Paired T-test shows that Vitros 5.1 FS and QuikRead CRP does not produces the same results.

    This study shows that QuikRead CRP is a user-friendly instrument that fits well in near patient testing. QuikRead CRP and Vitros 5.1 FS did not give the same results of P-CRP. This does not affect the results in regards to distinguish a viral infection (10-50 mg / L) from a bacterial infection (> 100 mg / L).

  • 261.
    Gagner, Viktor Ahlberg
    et al.
    University of Gothenburg, Sweden.
    Lundholm, Ida
    University of Gothenburg, Sweden.
    Garcia-Bonete, Maria-Jose
    University of Gothenburg, Sweden.
    Rodilla, Helena
    Chalmers University of Technology, Sweden.
    Friedman, Ran
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Zhaunerchyk, Vitali
    University of Gothenburg, Sweden.
    Bourenkov, Gleb
    DESY, Germany.
    Schneider, Thomas
    DESY, Germany.
    Stake, Jan
    Chalmers University of Technology, Sweden.
    Katona, Gergely
    University of Gothenburg, Sweden.
    Clustering of atomic displacement parameters in bovine trypsin reveals a distributed lattice of atoms with shared chemical properties2019In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 9, p. 1-14, article id 19281Article in journal (Refereed)
    Abstract [en]

    Low-frequency vibrations are crucial for protein structure and function, but only a few experimental techniques can shine light on them. The main challenge when addressing protein dynamics in the terahertz domain is the ubiquitous water that exhibit strong absorption. In this paper, we observe the protein atoms directly using X-ray crystallography in bovine trypsin at 100 K while irradiating the crystals with 0.5THz radiation alternating on and off states. We observed that the anisotropy of atomic displacements increased upon terahertz irradiation. Atomic displacement similarities developed between chemically related atoms and between atoms of the catalytic machinery. This pattern likely arises from delocalized polar vibrational modes rather than delocalized elastic deformations or rigid-body displacements. The displacement correlation between these atoms were detected by a hierarchical clustering method, which can assist the analysis of other ultra-high resolution crystal structures. These experimental and analytical tools provide a detailed description of protein dynamics to complement the structural information from static diffraction experiments.

  • 262.
    Gashi, Florina
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Bipacksedeln, till vilken nytta?2014Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [sv]

    Etthundratrettio miljoner läkemedelsförpackningar säljs årligen i Sverige. Varje förpackning inkluderar en bipacksedel om det specifika läkemedlet. Bipacksedeln är utformad utifrån EU-direktivet 92/27EEC. Cirka trettio procent av alla läkemedelsanvändare läser bipacksedeln. Anledningen till varför patienterna inte läser den, beror på att bipacksedelns text är svår läsa och förstå. Ungefär femtio procent av alla patienter förstår medicinska instruktioner. Det beror på individens utbildningsnivå, lägre utbildning gör det svårare att förstå kontexten i en text. Syftet med studien var att konstatera bipacksedelns värde och om denna främjar god läkemedelsanvändning. Metoden som användes var att söka efter vetenskapliga artiklar som objektivt svarade på syftet.

    Resultatet konstaterade att nyttan av en bipacksedel uppnås genom att folk läser den. Studier har visat att bipacksedeln blir mer läsvänlig om den innehåller ett mer lättförståeligt språk, färgade avsnitt, text med större bokstäver och symboler. Det kostar 100 till 130 miljoner kronor att producera bipacksedlar. En studie har visat att följsamheten av läkemedelsbehandling inte påverkas av bipacksedeln. Det har även konstaterats att bipacksedlar ibland kan minska följsamheten för behandlingar, eftersom de kan avskräcka patienter från att ta läkemedlet. Muntlig läkemedelsrådgivning har visat sig ge bättre följsamhet för patienter än enbart skriftlig information. Kombinationen av muntlig och skriftlig information har visat sig ge bäst informationsförståelse. De 130 miljoner kronorna bör därför möjligen investeras i att ge bättre muntlig information till patienter. För vidare studier bör en mer detaljerad information kring läkemedlens effekt lyftas fram tydligare i bipacksedlarna. 

  • 263.
    Gavlasova, Dagmar
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Studie av läkemedelssubstansers miljöfarliga egenskaper och effekt på miljö med fokus på ciprofloxacin, diklofenak och etinylestradiol2013Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [sv]

    Läkemedel är en grupp kemikalier med effekt på olika fysiologiska processer hos människa och djur. Den största källa för läkemedelsrester är avloppsvatten från reningsverk. Eliminering av läkemedelssubtanser i reningsverk är ofta inte fullständig och läkemedelsrester i naturen har påvisats. Läkemedelsrester i vattenmiljö kan bioakumuleras och utgör toxisk risk för vattenlevande organismer. Med den globala utvecklingen av samhället förväntas exponeringen för läkemedelsrester öka. Ciprofloxacin, diklofenak och etinylestradiol tillhör läkemedelsgrupper för vilka effekter på miljö har observerats. En ökad kunskap om substansernas miljöskadliga egenskaper kan ge ett bättre underlag vid miljöriskbedömningar. Syftet med arbetet är att utifrån aktuell litteratur sammanfatta den kunskap och fakta som idag finns om ciprofloxacin, diklofenak och etinylestradiol med avseende på dessa ämnens miljöfarliga egenskaper och miljöpåverkan. Efter sökning och genomgång av vetenskapliga artiklar och rapporter inom området läkemedel och miljö sammanställdes en litteratur översikt över kända miljöeffekter av substanserna ciprofloxacin, diklofenak och etinylestradiol. Apotekens Service AB databas över uthämtade läkemedl på apotek (Concise) användes för kartläggning av användning av ciprofloxacin, diklofenak och etinylestradiol i Kalmar län och Sverige totalt. Ciprofloxacin, diklofenak och etinylestradiol har påvisats i vattenmiljöer i Sverige och andra länder. Kinolon-resistenta bakterier har påvisats i miljö. Toxisk effekt av diklofenak på t ex gamar i Asien har observerats. Etinylestradiol i miljö orsakar störningar av reproduktionsförmåga hos fisk. Det finns idag ingen dokumentation om läkemedel i miljö som pekar på en risk för humanhälsa. Enskilda hushåll står för den största delen av läkemedelsflöde till miljö. Uppmätt koncentration av läkemedelsrester i miljö ligger ofta mellan 1 ng/L upp till några µg/L. I miljön återfinns substanser huvudsakligen i en mix av olika ämnen. Det är viktigt med fortsatt forskning kring läkemedel i miljö för att kunna bidra till bättre framtida kunskap.

  • 264.
    Geete, Järvekülg
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Fertilitet efter behandling av Hodgkins lymfom med olika kombinationer av cytostatika (ABVD och BECOPP)2018Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [sv]

    Hodgkins lymfom är en cancersjukdom som uppstår i det lymfatiska systemet och i Sverige är det ungefär 200 personer per år som insjuknar. Majoriteten av de insjuknade är mellan 15-34 år och ungefär 90% med diagnosen blir botade. Behandlingsformen för Hodgkins lymfom varierar beroende på stadie och då även vilka substanser som ingår i behandlingen. Alkylerande substanser, till exempel prokarbazin och cyklofosfamid, är substanser som är icke-cell-cykelspecifika och förhindrar DNA syntes. Detta kan leda till azoospermi hos männen och reducerad population av ursprungfolliklar hos kvinnor. På grund av dessa effekter var syftet med denna litteraturstudie att se om behandlingarna ABVD (en kombination av fyra olika cytostatika) och BEACOPP (en kombination av prednisolon samt sex olika cytostatika med större innehåll av alkylerare än ABVD) leder till en nedsatt fertilitet hos kvinnor och/eller män samt om fertiliteten återkommer efter avslutad behandling. Detta gjordes genom en litteraturstudie efter sökningar på PubMed där sju studier valdes ut efter inklusionskriterier och exklusionskriterier. Det kunde ses att spermiekvalitén minskade efter båda behandlingsformerna bland männen och att antalet behandlingscykler hade betydelse för hur nedsatt fertiliteten blev. Färre cykler med mindre intensiv behandling hade mindre effekt än fler cykler av mer intensiv behandling. De flesta männen återfick dock sin fertilitet inom fem år. För kvinnorna sågs ett snarlikt resultat där behandlingen BEACOPP orsakade försämrade värden av anti-müllerskt hormon (AMH) och en frånvaro av menstruationscykeln. Hos kvinnor var förekomsten av prematur ovarialsvikt (POF) korrelerat till ålder vid behandlingens start och antalet cykler administrerade.

  • 265.
    Georgoulia, Panagiota S.
    et al.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences. University of Gothenburg, Sweden.
    Bjelic, Sinisa
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Friedman, Ran
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Deciphering the molecular mechanism of FLT3 resistance mutations2020In: The FEBS Journal, ISSN 1742-464X, E-ISSN 1742-4658Article in journal (Refereed)
    Abstract [en]

    FMS-like tyrosine kinase 3 (FLT3) has been found to be mutated in 30% of acute myeloid leukaemia patients. Small-molecule inhibitors targeting FLT3 that are currently approved or still undergoing clinical trials are subject to drug resistance due to FLT3 mutations. How these mutations lead to drug resistance is hitherto poorly understood. Herein, we studied the molecular mechanism of the drug resistance mutations D835N, Y842S and M664I, which confer resistance against the most advanced inhibitors, quizartinib and PLX3397 (pexidartinib), using enzyme kinetics and computer simulations. In vitro kinase assays were performed to measure the comparative catalytic activity of the native protein and the mutants, using a bacterial expression system developed to this aim. Our results reveal that the differential drug sensitivity profiles can be rationalised by the dynamics of the protein-drug interactions and perturbation of the intraprotein contacts upon mutations. Drug binding induced a single conformation in the native protein, whereas multiple conformations were observed otherwise (in the mutants or in the absence of drugs). The end-point kinetics measurements indicated that the three resistant mutants conferred catalytic activity that is at least as high as that of the reference without such mutations. Overall, our calculations and measurements suggest that the structural dynamics of the drug-resistant mutants that affect the active state and the increased conformational freedom of the remaining inactive drug-bound population are the two major factors that contribute to drug resistance in FLT3 harbouring cancer cells. Our results explain the mechanism of drug resistance mutations and can aid to the design of more effective tyrosine kinase inhibitors.

  • 266.
    Georgoulia, Panagiota S.
    et al.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Glykos, Nicholas M.
    University of Thrace, Greece.
    Molecular simulation of peptides coming of age: accurate prediction of folding, dynamics and structures2019In: Archives of Biochemistry and Biophysics, ISSN 0003-9861, E-ISSN 1096-0384, Vol. 664, no March, p. 76-88Article in journal (Refereed)
    Abstract [en]

    The application of molecular dynamics simulations to study the folding and dynamics of peptides has attracted a lot of interest in the last couple of decades. Following the successful prediction of the folding of several proteins using molecular simulation, foldable peptides emerged as a favourable system mainly due to their application in improving protein structure prediction methods and in drug design studies. However, their performance is inherently linked to the accuracy of the empirical force fields used in the simulations, whose optimisation and validation is of paramount importance. Here we review the most important findings in the field of molecular peptide simulations and highlight the significant advancements made over the last twenty years. Special reference is made on the simulation of disordered peptides and the remaining challenge to find a force field able to describe accurately their conformational landscape.

  • 267.
    Georgoulia, Panagiota S.
    et al.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Todde, Guido
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Bjelic, Sinisa
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Friedman, Ran
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    The catalytic activity of Abl1 single and compound mutations: Implications for the mechanism of drug resistance mutations in chronic myeloid leukaemia2019In: Biochimica et Biophysica Acta - General Subjects, ISSN 0304-4165, E-ISSN 1872-8006, Vol. 1863, no 4, p. 732-741Article in journal (Refereed)
    Abstract [en]

    Background

    Abl1 is a protein tyrosine kinase whose aberrant activation due to mutations is the culprit of several cancers, most notably chronic myeloid leukaemia. Several Abl1 inhibitors are used as anti-cancer drugs. Unfortunately, drug resistance limits their effectiveness. The main cause for drug resistance is mutations in the kinase domain (KD) of Abl1 that evolve in patients. The T315I mutation confers resistance against all clinically-available inhibitors except ponatinib. Resistance to ponatinib can develop by compound (double) mutations.

    Methods

    Kinetic measurements of the KD of Abl1 and its mutants were carried out to examine their catalytic activity. Specifically, mutants that lead to drug resistance against ponatinib were considered. Molecular dynamics simulations and multiple sequence analysis were used for explanation of the experimental findings.

    Results

    The catalytic efficiency of the T315I pan-resistance mutant is more than two times lower than that of the native KD. All ponatinib resistant mutations restore the catalytic efficiency of the enzyme. Two of them (G250E/T315I and Y253H/E255V) have a catalytic efficiency that is more than five times that of the native KD.

    Conclusions

    The measurements and analysis suggest that resistance is at least partially due to the development of a highly efficient kinase through subsequent mutations. The simulations highlight modifications in two structurally important regions of Abl1, the activation and phosphate binding loops, upon mutations.

    General significance

    Experimental and computational methods were used together to explain how mutations in the kinase domain of Abl1 lead to resistance against the most advanced drug currently in use to treat chronic myeloid leukaemia.

  • 268.
    Georgsson, Jonathan
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Är CTLA-4-inhibitorn ipilimumab bättre som monoterapi eller i kombination med andra läkemedel hos patienter med metastaserat malignt melanom?2016Independent thesis Basic level (university diploma), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    Malignant melanoma is a growing problem with more and more people in Sweden and the world suffering from this cancer. Malignant melanoma is a disease that when discovered in time can be treated successfully with surgical methods, but the real challenge lies in treating the disease after its spread. Treatment in the past for advanced malignant melanoma has been unsuccessful with no positive effect on overall survival. However, in the last couple of years, new treatment has arrived with focus on priming the immune system to eradicate the tumors. One new drug is the CTLA-4 inhibitor ipilimumab that is given as intravenous infusion. CTLA-4 is a protein located on regulatory T-cells and that is upregulated on activated cytotoxic T-cells. This protein mediates an inhibitory signal that attenuates T-cell-activation.  Treatment with the CTLA-4 inhibitor has been shown to increase overall survival. However, not much is known about how well ipilimumab synergizes with other drugs used for treatment of malignant melanoma.

     

    This is a literature study with the aim to evaluate if ipilimumab is used best as monotherapy or if it is of better use as part of a combination therapy. Search was made in PubMed with the key-words "Ipilimumab", "Ipilimumab treatment", CTLA-4 inhibitor" and "treatment malignant melanoma”. Six articles were chosen and each of these analyzed the effect of ipilimumab alone or combined with other agents against malignant melanoma.

     

    The combination of ipilimumab and the alkylating agent dacarbazine was shown to have a better impact on overall survival compared with monotherapy with dacarbazine, but this combination also showed an increase in serious adverse events. Ipilimumab also showed to work in synergy with both the PD-1-inhibitor nivolumab and the granulocyte macrophage colony-stimulating factor (GM-CSF) sargramostim. Combination with sargramostim was also shown to decrease the amount of serious adverse events. Combination with a gp100 peptide vaccine failed to show any positive effects on overall survival. Also prophylactic treatment with budesonide showed no further gain in overall survival. The effect of ipilimumab was found to have a dose-ranging effect, with higher dose treatment having a better effect but also with more serious adverse events.

     

    The results of this literature study showed that ipilimumab has a better effect with higher dose and that it can work in synergy with other agents such as nivolumab and sargramostim. Results also showed that occurring adverse effects during treatment with ipilimumab may be treated with systemic glucocorticoids that did not affect the tumor-killing ability of ipilimumab. These results should be evaluated in bigger studies and with longer follow up time.

  • 269.
    Geraldsson, Amanda
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Jämförelse av antigenicitet och biverkningsprofil mellan Gardasil och Cervarix2017Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    The purpose of this diploma work project was to determine if one of the HPV-vaccines, Cervarix-bHPV or Gardasil-qHPV, has lower safety adverse events- SAE.

    There are more than 150 different types of human papillomavirus, which infect mucosal cells, mostly in the genital tract. The virus infects through sexual-contact, there are high-risk HPV-types such as HPV16/18, which are oncogenic and low-risk HPV-types such as HPV6/11, which cause genital warts. The goal for the world health organization-WHO is to get the HPV-vaccines to all women around the globe. Most common age for the vaccinées is 12-years. Headache, pain, erythema and swelling are very common adverse events for both of vaccines. Common adverse events are fever and nausea. In addition, Post Orthostatic Tachycardia Syndrome-POTS and Complex Regional Pain Syndrome-CRPS have been reported, mostly from Japan and Denmark. European medicines agency-EMA made a statement that the HPV-vaccines are not the cause of the POTS or CRPS (2015), because the profile of the symptoms from Japan and Denmark do not correlate with symptom profiles of POTS or CRPS. In Denmark’s case, EMA suggest that some of the cases resembles symptoms of chronic fatigue syndrome-CFS and not POTS.

    This diploma work project was made with the help of Pubmed, with the words “Gardasil”, “Cervarix” and “safety”. Four articles were chosen from the search. 

    The authors of the first article examined the effect of booster dose of bHPV or qHPV to girls age 12-13, who already had received two doses of qHPV. In the second article, two doses of bHPV were compared with two or three doses of qHPV in 9-14 year-old girls in order to determine if bHPV were equal or superior to two or three doses of qHPV. The third and fourth articles are follow-up studies of the second one, the third up to 48 months and the fourth up to 60 months. These articles were studying the sero-positivity in the vaccinated subjects over time.

    When comparing study one and two, the bHPV safety profiles differences were seen in the safety adverse events in both local and general or systemic adverse events. There was a difference of adverse events between (article 2) three doses of qHPV to (article 1) booster dose of qHPV. Sero-positivity showed that bHPV induced high titres of HPV 16 and 18 antibodies while qHPV vaccine also induced high amounts of HPV 16 antibodies but low amounts of HPV 18 antibodies. About 20 % of the women in qHPV-groups lost sero-positivity by month 60. bHPV and qHPV vaccines were similar regarding adverse events. The vaccines had equal types of local and systemic or general adverse events. Sero-positivity was higher in subject vaccinated with bHPV compared to qHPV, with the highest decline in sero-positivity for anti-HPV 18.

    The conclusions of this literature study is that the qHPV vaccine protects against low-risk and high-risk HPV-types, while the bHPV vaccine has longer duration.

  • 270.
    Gidvall, Sanna
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Finns det ett samband mellan vitamin D-status och atopiskt eksem?2018Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    The aim of this study was to determined the relationship between atopic eczema and vitamin D. The hypothesis that were tested are:” A higher level of vitamin D in blood serum is negatively correlated with atopic eczema”. The studyis a literature review: seven scientific articles on the subject vitamin D and atopic eczema are used in this essay. The work is based on a 2016 meta-analysis by Kim et althat addressed the same issue. The results show that two out of seven articles indicate a negative association between vitamin D and atopic eczema. In the other five studies no significant result is evident. 

    The conclusion is that there appears to be no direct link between vitamin D levels and atopic eczema. This is an opposite outcome to the Kim et almeta-analysis.

  • 271.
    Giovannoli, Cristina
    et al.
    Univ Turin, Italy.
    Passini, Cinzia
    Univ Turin, Italy.
    Di Nardo, Fabio
    Univ Turin, Italy.
    Anfossi, Laura
    Univ Turin, Italy.
    Baggiani, Claudio
    Univ Turin, Italy.
    Nicholls, Ian A.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Affinity Capillary Electrochromatography of Molecularly Imprinted Thin Layers Grafted onto Silica Capillaries Using a Surface-Bound Azo-Initiator and Living Polymerization2018In: Polymers, ISSN 2073-4360, E-ISSN 2073-4360, Vol. 10, no 2, article id 192Article in journal (Refereed)
    Abstract [en]

    Molecularly imprinted thin layers were prepared in silica capillaries by using two different surface polymerization strategies, the first using 4,4-azobis(4-cyanovaleric acid) as a surface-coupled radical initiator, and the second, S-carboxypropyl-S'-benzyltrithiocarbonate as a reversible addition-fragmentation chain transfer (RAFT) agent in combination with 2,2-azobisisobutyronitrile as a free radical initiator. The ability to generate imprinted thin layers was tested on two different polymerization systems: (i) a 4-vinylpyridine/ethylene dimethacrylate (4VP-EDMA) in methanol-water solution with 2,4,5-trichlorophenoxyacetic acid (2,4,5-T) as a template; and (ii) methacrylic acid/ethylene dimethacrylate (MAA-EDMA) in a chloroform solution with warfarin as the template molecule. The binding properties of the imprinted capillaries were studied and compared with those of the corresponding non-imprinted polymer coated capillaries by injecting the template molecule and by measuring its migration times relative to a neutral and non-retained marker. The role of running buffer hydrophobicity on recognition was investigated by studying the influence of varying buffer acetonitrile concentration. The 2,4,5-T-imprinted capillary showed molecular recognition based on a reversed phase mechanism, with a decrease of the template recognition in the presence of higher acetonitrile content; whereas warfarin-imprinted capillaries showed a bell-shaped trend upon varying the acetonitrile percentage, illustrating different mechanisms underlying imprinted polymer-ligand recognition. Importantly, the results demonstrated the validity of affinity capillary electrochromatography (CEC) to screen the binding properties of imprinted layers.

  • 272.
    Golker, Kerstin
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Fundamental Studies on Molecularly Imprinted Materials2014Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The thesis focuses on fundamental studies aimed at elucidating factors that influence molecularly imprinted polymer (MIP) formation and ligand recognition. To this end, a series of computational techniques, in particular chemometrics and molecular dynamics (MD) in conjunction with polymer synthesis and physical characterization studies have been employed.

     

    In Paper I, the multivariate analysis method principal component analysis (PCA) was used to investigate the role of incubation media on polymer-ligand recognition, and results highlighted the importance of several solvent parameters on recognition. In Paper II, all-component MD simulations were used to examine the role of polymerization mixture stoichiometry on MIP-template recognition. Correlations between nature and extent of template complexation and recognition were observed. The influence of the acidic functionality of the methacrylic acid used in these polymers on polymer-template recognition and morphology was examined in Paper III. PCA was then used in Paper IV to identify relationships between interactions in the pre-polymerization mixture, polymer functionality, recognition and morphology using the polymers described in Paper II and III.

  • 273.
    Golker, Kerstin
    et al.
    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.
    Olsson, Gustaf D.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Rosengren, Annika M.
    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.
    Influence of composition and morphology on template recognition in molecularly imprinted polymers2013In: Macromolecules, ISSN 0024-9297, E-ISSN 1520-5835, Vol. 46, no 4, p. 1408-1414Article in journal (Refereed)
    Abstract [en]

    A combination of theoretical and experimental studies has provided correlations between molecularly imprinted polymer composition, morphology, and recognition behavior obtained using a series of bupivacaine-imprinted methacrylic acid (MAA)–ethylene glycol dimethacrylate copolymers differing in molar ratios of the respective monomers. Results extracted from analysis of molecular dynamics (MD) trajectory data demonstrated that stability and frequency of interactions between bupivacaine and the monomers in the prepolymerization phase were strongly affected by minor changes in polymer composition, which in turn affected binding site affinity and heterogeneity of the imprinted polymers. Moreover, through the characterization of polymer morphology, we show that higher molar fractions of MAA resulted in polymeric materials with increased pore size, a feature that enhanced the binding capacity of the polymers. Furthermore, the results presented point at the strength of MD for predicting MIP-template binding capacity and affinity.

  • 274.
    Golker, Kerstin
    et al.
    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.
    Rosengren, Annika M.
    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.
    A Functional Monomer Is Not Enough: Principal Component Analysis of the Influence of Template Complexation in Pre-Polymerization Mixtures on Imprinted Polymer Recognition and Morphology2014In: International Journal of Molecular Sciences, ISSN 1422-0067, E-ISSN 1422-0067, Vol. 15, no 11, p. 20572-20584Article in journal (Refereed)
    Abstract [en]

    In this report, principal component analysis (PCA) has been used to explore the influence of template complexation in the pre-polymerization phase on template molecularly imprinted polymer (MIP) recognition and polymer morphology. A series of 16 bupivacaine MIPs were studied. The ethylene glycol dimethacrylate (EGDMA)-crosslinked polymers had either methacrylic acid (MAA) or methyl methacrylate (MMA) as the functional monomer, and the stoichiometry between template, functional monomer and crosslinker was varied. The polymers were characterized using radioligand equilibrium binding experiments, gas sorption measurements, swelling studies and data extracted from molecular dynamics (MD) simulations of all-component pre-polymerization mixtures. The molar fraction of the functional monomer in the MAA-polymers contributed to describing both the binding, surface area and pore volume. Interestingly, weak positive correlations between the swelling behavior and the rebinding characteristics of the MAA-MIPs were exposed. Polymers prepared with MMA as a functional monomer and a polymer prepared with only EGDMA were found to share the same characteristics, such as poor rebinding capacities, as well as similar surface area and pore volume, independent of the molar fraction MMA used in synthesis. The use of PCA for interpreting relationships between MD-derived descriptions of events in the pre-polymerization mixture, recognition properties and morphologies of the corresponding polymers illustrates the potential of PCA as a tool for better understanding these complex materials and for their rational design.

  • 275.
    Golker, Kerstin
    et al.
    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. Bioorganic & Biophysical Chemistry Laboratory.
    Wiklander, Jesper G.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Rosengren, Annika M.
    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.
    Hydrogen bond diversity in the pre-polymerization stage contributes to morphology and MIP-template recognition–MAA versus MMA2015In: European Polymer Journal, ISSN 0014-3057, E-ISSN 1873-1945, Vol. 66, p. 558-568Article in journal (Refereed)
    Abstract [en]

    This report demonstrates that the diversity of hydrogen bond interactions present in molecularly imprinted polymer pre-polymerization mixtures, typically associated with binding-site heterogeneity, can also contribute to morphological characteristics that may influence polymer–template recognition. Comparisons have been made between a series of bupivacaine molecularly imprinted methacrylic acid (MAA)–ethylene glycol dimethacrylate (EGDMA) copolymers and a series of analogous methyl methacrylate (MMA)–EGDMA copolymers using comprehensive molecular dynamics studies of the respective pre-polymerization mixtures, template–polymer binding studies and detailed BET surface area and BJH porosity analyses. The role of the carboxylic acid functionality of MAA, and in particular the acidic proton, in generating morphological features conducive to analyte access (slit-like rather than ink bottle-like structures) and recognition is discussed.

  • 276.
    Golker, Kerstin
    et al.
    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.
    The effect of crosslinking density on molecularly imprinted polymer morphology and recognition2016In: European Polymer Journal, ISSN 0014-3057, E-ISSN 1873-1945, Vol. 75, p. 423-430Article in journal (Refereed)
    Abstract [en]

    In this report, the crosslinking density of bupivacaine molecularly imprinted methacrylic acid (MAA)-ethylene glycol dimethacrylate (EGDMA) copolymers was investigated through replacement of EGDMA by methyl methacrylate (MMA). The effects were examined using a series of full-scale MD simulations of pre-polymerization mixtures, equilibrium rebinding studies on the corresponding synthesized polymers and morphology characterization through nitrogen sorption measurements. While the extent of hydrogen bonding between the functional monomer MAA and bupivacaine observed in the MD pre-polymerization mixtures was comparable in each of the systems studied, the decrease in degree of crosslinking impacted directly on polymer morphology as observed in BET and BJH studies of surface area and porosity. Further, decreases in the crosslinking density induced reductions in template rebinding capacity as seen from a series of radio-ligand binding studies, demonstrating the importance of crosslinking on the performance of molecularly imprinted MAA-EGDMA copolymers, the polymer system most commonly used in molecular imprinting science and technology. (C) 2016 Elsevier Ltd. All rights reserved.

  • 277.
    Golker, Kerstin
    et al.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences. Uppsala university.
    Olsson, Gustaf D.
    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.
    The influence of a methyl substituent on molecularly imprinted polymer morphology and recognition – Acrylic acid versus methacrylic acid2017In: European Polymer Journal, ISSN 0014-3057, E-ISSN 1873-1945, Vol. 92, p. 137-149Article in journal (Refereed)
    Abstract [en]

    In this report, we have investigated factors contributing to the morphology and template recognition of bupivacaine-imprinted copolymers of methacrylic acid (MAA) and ethyleneglycol dimethacrylate (EGDMA). To this end, MAA, the most commonly used functional monomer in non-covalent molecular imprinting protocols, was compared and contrasted with the closely related acrylic acid (AA) in terms of polymer morphologies, recognition characteristics, and molecular level events in the corresponding pre-polymerization mixtures. Two series of analogous bupivacaine-imprinted EGDMA-copolymers containing increasing fractions of either AA or MAA were studied through all-component MD simulations in the pre-polymerization phase, equilibrium binding experiments on corresponding synthesized polymers and morphology characterization by N2-sorption measurements. A higher degree of hydrogen bonding frequency between respective functional monomer and bupivacaine was recorded for the mixtures containing AA compared to those containing MAA. In contrast, results from binding experiments demonstrated higher binding capacities for the polymers prepared with MAA than for those prepared with AA, which is explained by differences in polymer morphology. The surface areas and pore volumes of the AA-polymers were higher than for the MAA-polymers and the overall pore structure in the AA-polymers was ink-bottle shaped while the pores in the MAA-polymers were slit-shaped. We suggest that the methyl substituent of MAA contributes to differences in the reaction kinetics for AA and MAA during polymerization and resulted in different morphologies, in particular pore shape, which affected mass-transfer and consequently the binding qualities of the materials. © 2017 Elsevier Ltd

  • 278.
    Grahn, Karin
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Hur uppfattar farmaceuter tillgänglig information om patienters aktuella läkemedel och hur ser de på övergången till en gemensam nationell läkemedelslista?2017Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    Doctors, nurses, pharmacists, patients and next of kin are all parts of the chain that is needed to make sure that the use of medication is safe and appropriate for the patient. That many people involved and in many different settings can make the use of medication difficult to manage. In the year 2014 there were 102 913 130 prescriptions made out to patients in Sweden. Up to the year 2014 850 000 corrections had been made to prescriptions with faults in them by pharmacists each year. To correct prescriptions is an essential part of the pharmacist’s obligations and responsibility, a responsibility that is regulated in Swedish law. The pharmacist is the last part of the chain that has the possibility to adjust anything that is wrong with medications and the use of it before it is in the patient’s own hands. The access to a nationally shared medication list for all involved parties might solve some of the problems that faces the responsible parties when it comes to dealing with patients and their new and ongoing medications and in that way be able to increase the safety around mediation for the patient in need. Although the survey conducted as part of this paper focuses on pharmacists the background tries to explain in what way the different professions come in contact with medicines and how they would perhaps benefit from a shared list. The paper also tries to give a little insight to what kind of problems there could be related to prescriptions. In Sweden we have come a rather long way in the use of computers and the use of internet in the field of eHealth compared to other countries. The paper tries to show how the problem surrounding prescription of medicine is handled in the other countries of Scandinavia. Earlier studies have been conducted that looks at shared lists from the doctors view and also studies have been conducted that looks upon eHealth for patients partly in view of shared medication lists. No studies have been found that looks specifically at how pharmacists feel about it and how such a list would benefit them in their work to secure patient safety, hence this paper. In order to reach the papers purpose a survey was performed with pharmacists employed at different pharmacies in the southern part of Sweden. The result of the survey showed that there are indeed problems with prescriptions in the prescription repository and the majority of the pharmacists agreed that a shared medication list could help them in their work to secure patient safety when releasing prescribed medication. Although the pharmacist agreed for the most part in the benefits of such a list they did not know if it would solve all problems, which is for the future to decide.

  • 279.
    Granberg, Ebba
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Fleromättade fetter, torra ögon och Sjögrens syndrom: Kan en kost rik på omega 3 och 6 lindra symtomen vid Sjögrens syndrom och torra ögon?2017Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    Introduction: Dry eye syndrome (DES) and Sjögren ́s syndrome (SjS) are inflammatory diseases that affect the eyes. DES affects the lacrimal glands functional unit, causing eye pain and blurred vision. SjS is a chronical autoimmune disease that causes damage to tear and salivary glands. It leads to clinical symptoms in the form of mouth and eye irritation. Essential fatty acids form pro-inflammatory and anti-inflammatory cytokines that can help in the treatment of these diseases. Method and purpose: A literature study was performed to study if essential fatty acids can relieve the symptoms of DES and SjS. Results: The results for the studies showed results on OSDI, Schirmer ́s test, BUT, IL- 17, tear osmolarity, tear volume, unstimulated salivary flow, stimulated salivary flow, depth of probing, van Bijsterveld ́s score and flourscein staining. Discussion: The result shows significant differences for certain doses of n-3 and n-6. What separates the results are the different doses of fatty acids and what their placebo controls took. OSDI showed major differences in patients with DES but only in one group of patients with SjS who took n-3 for treating dry mouth. Schirmer ́s test and BUT showed an increase in patients with mild and moderate DES but not in patients with SjS. Patients with SjS showed improvements in stimulated salivary flow, dry mouth OSDI, PGE1 levels and flourscein staining, while some studies did not show any significant improvements in any measurement variables. It may be due to the intake of fatty acids, disease states or the length of treatment. Conclusion: Some people may get improved symptoms of taking n- 3 or n-6 supplements, but the differences are not always statistically significant for the studies.

  • 280.
    Granung, Julia
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Optimering av rensningsprocessen för hel svartpeppar och timjan2017Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    The main aim of the work presented in this thesis was to investigate the cleansing process for thyme and whole black pepper in cooperation with Santa Maria AB. This by investigate the quality of the purged raw material, but also whether a double cleansing is necessary, as there is a risk that unnecessarily cleaning is causing a significant amount of waste. Analysis of what is removed could identify improvements that are of both financial and environmental importance for the company.

    The analysis of thyme and black pepper was made after initially comparing the different fractions with a double cleansed premium product (reference). Among the methods used were sensory evaluation, bulk measurements and the total content of volatile oils, through hydro distillation, and their volatile profile, identified by GCMS.

    The results found for thyme showed that the product demands a double cleansing. One fraction that was formed in the cleansing process showed the same quality as the reference spice for all parameters except the bulk weight, which was higher than the reference. It was found that the separated fraction can replace grinded thyme, which is used in several blends at Santa Maria AB.

    The results obtained for black pepper showed a potential for Santa Maria to single clean this product. The fraction that was formed during cleansing consisted mostly of shell. This fraction did not have the same quality that Santa Maria demanded and is therefore not suitable to use. 

  • 281.
    Gränse, Agnes
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Jämförelse mellan markörer för funktionellt järnstatus på Siemens Advia 2120 och Sysmex XN-1000 2014Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [sv]

    Syre transporteras från lungorna, via blodet bundet till erytrocyternas hemoglobin, till kroppens alla celler. En hemoglobinkoncentration i blodet under referensintervallet definieras som anemi och påverkar hela kroppen och försämrar den fysiska prestationsförmågan. Järnbristanemi är en anemi med otillräcklig järntillförsel till benmärgen på grund av tomma järnförråd (absolut järnbrist) eller försvårat järnutnyttjande (funktionell järnbrist). Analysparametern HYPO på analysinstrumentet Advia 2120 (Siemens) mäter andelen hypokroma erytrocyter (erytrocyter med lågt hemoglobininnehåll) och anses vara en av de bästa parametrarna för att påvisa funktionell järnbrist. Analysparametern Hypo-He på analysinstrumentet XN-1000 (Sysmex) är en forskningsparameter för samma ändamål. Syftet med detta arbete var att jämföra markörer för funktionellt järnstatus och utvärdera om analysen HYPO på Advia 2120 kan ersättas med Hypo-He på XN-1000. Fyrtiofyra patientprover, på vilka HYPO var beställt, analyserades, först på XN-1000 och därefter på Advia 2120. En linjär regressionmodell gjordes för att beskriva korrelationen mellan analyserna HYPO och Hypo-He. Imprecisionen för analysen Hypo-He beräknades genom inom-serie- och total-serie-imprecision. Korrelationen mellan analyserna var måttligt stark (r = 0,7185 (absoluta värden) och r = 0,8081 (logaritmerade värden)), dock med många analysresultat inom det lägre området. Variationskoefficienten för Hypo-He beräknades till mellan 0 % - 9,5 %. För att kunna avgöra om Hypo-He kan ersätta HYPO som indikator på funktionell järnbrist krävs kompletterande studier på välkaraktäriserade patientprover med varierande analysvärden inkluderande värden för HYPO på mer än 10 %.

  • 282.
    Guo, Ming
    et al.
    Zhejiang Agr & Forestry Univ, Peoples Republic of China.
    Hu, Yinglu
    Zhejiang Agr & Forestry Univ, Peoples Republic of China.
    Wang, Lixia
    Zhejiang Agr & Forestry Univ, Peoples Republic of China.
    Brodelius, Peter E.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Sun, Liping
    Zhejiang Agr & Forestry Univ, Peoples Republic of China.
    A facile synthesis of molecularly imprinted polymers and their properties as electrochemical sensors for ethyl carbamate analysis2018In: RSC Advances, ISSN 2046-2069, E-ISSN 2046-2069, Vol. 8, no 69, p. 39721-39730Article in journal (Refereed)
    Abstract [en]

    New molecularly imprinted polymers (MIPs), which exhibit specific recognition of ethyl carbamate (EC) have been synthesized and studied. In this process, EC was the template molecule and -cyclodextrin derivatives were employed as functional monomers in the molecular imprinting technique (MIT). An EC molecularly imprinted sensor (EC-MIS) was prepared by using MIT surface modification. The EC-MIS was characterized by cyclic voltammetry, electrochemical impedance spectroscopy and differential pulse voltammetry. EC detection performance, binding parameters and dynamics mechanism were investigated. The result showed that the synthetic route designed was appropriate and that new MIP and EC-MIS were successfully prepared. The EC-MIS exhibited a good molecular recognition of EC. A linear relationship between current and EC concentration was observed using cyclic voltammetry and the detection limit was 5.86 g L-1. The binding constant (K = 4.75 x 10(6) L mol(-1)) between EC and the EC-MIS, as well as, the number of binding sites (n = 1.48) has been determined. The EC-MIS recognition mechanism for the EC is a two-step process. The sensor was applied for the determination of EC in Chinese yellow wines, and the results were in good agreement with the gas chromatography-mass spectrometry (GC-MS) method.

  • 283.
    Guo, Ming
    et al.
    Zhejiang A & F University, China.
    Lu, Xiaowang
    Zhejiang A & F University, China.
    Wang, Yan
    Zhejiang A & F University, China.
    Brodelius, Peter E.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Comparison of the interaction between lactoferrin and isomeric drugs2017In: Spectrochimica Acta Part A - Molecular and Biomolecular Spectroscopy, ISSN 1386-1425, E-ISSN 1873-3557, Vol. 173, p. 593-607Article in journal (Refereed)
    Abstract [en]

    The binding properties of pentacyclic triterpenoid isomeric drugs, i.e. ursolic acid (UA) and oleanolic acid (OA), to bovine lactoferrin (BLF) have been studied by molecule modeling, fluorescence spectroscopy, UV-visible absorbance spectroscopy and infrared spectroscopy (IR). Molecular docking, performed to reveal the possible binding mode or mechanism, suggested that hydrophobic interaction and hydrogen bonding play important roles to stabilize the complex. The results of spectroscopic measurements showed that the two isomeric drugs both strongly quenched the intrinsic fluorescence of BLF through a static quenching procedure although some differences between UM and OA binding strength and non-radiation energy transfer occurred within the molecules. The number of binding sites was 3.44 and 3.10 for UA and OA, respectively, and the efficiency of Forster energy transfer provided a distance of 0.77 and 1.21 nm for UA and OA, respectively. The conformation transformation of BLF affected by the drugs conformed to the "all-or-none" pattern. In addition, the changes of the ratios of alpha-helices, beta-sheets and beta-turns of BLF during the process of the interaction were obtained. The results of the experiments in combination with the calculations showed that there are two modes of pentacyclic triterpenoid binding to BLF instead of one binding mode only governed by the principle of the lowest bonding energy.

  • 284.
    Guo, Ming
    et al.
    Zhejiang Agr & Forestry Univ, Peoples Republi of China.
    Wang, Xiaomeng
    Zhejiang Agr & Forestry Univ, Peoples Republi of China.
    Lu, Xiaowang
    Zhejiang Agr & Forestry Univ, Peoples Republi of China.
    Wang, Hongzheng
    Zhejiang Agr & Forestry Univ, Peoples Republi of China.
    Brodelius, Peter E.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    alpha-Mangostin Extraction from the Native Mangosteen (Garcinia mangostana L.) and the Binding Mechanisms of alpha-Mangostin to HSA or TRF2016In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 11, no 9, article id e0161566Article in journal (Refereed)
    Abstract [en]

    In order to obtain the biological active compound, alpha-mangostin, from the traditional native mangosteen (Garcinia mangostana L.), an extraction method for industrial application was explored. A high yield of a-mangostin (5.2%) was obtained by extraction from dried mangosteen pericarps with subsequent purification on macroporous resin HPD-400. The chemical structure of alpha-mangostin was verified mass spectrometry (MS), nuclear magnetic resonance (H-1 NMR and C-13 NMR), infrared spectroscopy (IR) and UV-Vis spectroscopy. The purity of the obtained alpha-mangostin was 95.6% as determined by HPLC analysis. The binding of native alpha-mangostin to human serum albumin (HSA) or transferrin (TRF) was explored by combining spectral experiments with molecular modeling. The results showed that amangostin binds to HSA or TRF as static complexes but the binding affinities were different in different systems. The binding constants and thermodynamic parameters were measured by fluorescence spectroscopy and absorbance spectra. The association constant of HSA or TRF binding to alpha-mangostin is 6.4832x10(5) L/mol and 1.4652x10(5) L/mol at 298 K and 7.8619x10(5) L/mol and 1.1582x10(5) L/mol at 310 K, respectively. The binding distance, the energy transfer efficiency between alpha-mangostin and HSA or TRF were also obtained by virtue of the Forster theory of non-radiation energy transfer. The effect of alpha-mangostin on the HSA or TRF conformation was analyzed by synchronous spectrometry and fluorescence polarization studies. Molecular docking results reveal that the main interaction between amangostin and HSA is hydrophobic interactions, while the main interaction between alpha-mangostin and TRF is hydrogen bonding and Van der Waals forces. These results are consistent with spectral results.

  • 285.
    Gustafson, Elisabet
    et al.
    Uppsala University Hospital, Sweden.
    Asif, Sana
    Uppsala University, Sweden.
    Kozarcanin, Huda
    Uppsala University, Sweden.
    Elgue, Graciela
    Uppsala University, Sweden.
    Meurling, Staffan
    Uppsala University Hospital, Sweden.
    Nilsson Ekdahl, Kristina
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Nilsson, Bo
    Uppsala University, Sweden.
    Control of IBMIR Induced by Fresh and Cryopreserved Hepatocytes by Low Molecular Weight Dextran Sulfate Versus Heparin2017In: Cell Transplantation, ISSN 0963-6897, E-ISSN 1555-3892, Vol. 26, no 1, p. 71-81Article in journal (Refereed)
    Abstract [en]

    Rapid destruction of hepatocytes after hepatocyte transplantation has hampered the application of this procedure clinically. The instant blood-mediated inflammatory reaction (IBMIR) is a plausible underlying cause for this cell loss. The present study was designed to evaluate the capacity of low molecular weight dextran sulfate (LMW-DS) to control these initial reactions from the innate immune system. Fresh and cryopreserved hepatocytes were tested in an in vitro whole-blood model using ABO-compatible blood. The ability to elicit IBMIR and the capacity of LMW-DS (100 mu g/ml) to attenuate the degree of activation of the cascade systems were monitored. The effect was also compared to conventional anticoagulant therapy using unfractionated heparin (1 IU/ml). Both fresh and freeze thawed hepatocytes elicited IBMIR to the same extent. LMW-DS reduced the platelet loss and maintained the cell counts at the same degree as unfractionated heparin, but controlled the coagulation and complement systems significantly more efficiently than heparin. LMW-DS also attenuated the IBMIR elicited by freeze thawed cells. Therefore, LMW-DS inhibits the cascade systems and maintains the cell counts in blood triggered by both fresh and cryopreserved hepatocytes in direct contact with ABO-matched blood. LMW-DS at a previously used and clinically applicable concentration (100 mu g/ml) inhibits IBMIR in vitro and is therefore a potential IBMIR inhibitor in hepatocyte transplantation.

  • 286.
    Gustafson, Elisabet
    et al.
    Uppsala Univ Hospital, Sweden.
    Hamad, Osama A.
    Uppsala University, Sweden.
    Deckmyn, Hans
    Katholieke Univ Leuven, Belgium.
    Barbu, Andreea
    Uppsala University, Sweden.
    Nilsson Ekdahl, Kristina
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Nilsson, Bo
    Uppsala University, Sweden.
    Exposure of von Willebrand Factor on Isolated Hepatocytes Promotes Tethering of Platelets to the Cell Surface2019In: Transplantation, ISSN 0041-1337, E-ISSN 1534-6080, Vol. 103, no 8, p. 1630-1638Article in journal (Refereed)
    Abstract [en]

    Background. Hepatocyte transplantation (Hctx) is a potentially attractive method for the treatment of acute liver failure and liver-based metabolic disorders. Unfortunately, the procedure is hampered by the instant blood-mediated inflammatory reaction (IBMIR), a thromboinflammatory response elicited by the vascular innate immune system, causing activation of the coagulation and complement systems and clearance of transplanted cells. Observations have also revealed platelets adhered to the surface of the hepatocytes (Hc). To establish Hctx as a clinical treatment, all factors that trigger IBMIR need to be identified and controlled. This work explores the expression of von Willebrand factor (VWF) on isolated Hc resulting in tethering of platelets. Methods. VWF on Hc was studied by flow cytometry, confocal microscopy, immunoblot, and real-time polymerase chain reaction. Interaction between Hc and platelets was studied in a Chandler loop model. Adhesion of platelets to the hepatocyte surface was demonstrated by flow cytometry and confocal microscopy. Results. Isolated Hc constitutively express VWF on their cell surface and mRNA for VWF was found in the cells. Hc and platelets, independently of coagulation formed complexes, were shown by antibody blocking studies to be dependent on hepatocyte-associated VWF and platelet-bound glycoprotein Ib alpha. Conclusions. VWF on isolated Hc causes, in contact with blood, adhesion of platelets, which thereby forms an ideal surface for coagulation. This phenomenon needs to be considered in hepatocyte-based reconstitution therapy and possibly even in other settings of cell transplantation.

  • 287.
    Gustafson, Hanna
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Hur effektiv och säker är fingolimod vid behandling av multipel skleros jämfört med natalizumab?2013Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [sv]

    Multipel skleros (MS) är en kronisk immunologisk sjukdom som slår på centrala nervsystemet (CNS) och kan leda till minskad neurologisk funktion. I Sverige finns 17 500 personer som fått en MS-diagnos. Den vanligaste åldern för insjuknande är 20-40 år och sjukdomen är dubbelt så vanlig bland kvinnor som bland män. Om patienterna inte får behandling finns risk för kraftiga funktionsnedsättningar. Syftet med detta arbete var att undersöka effekten och säkerheten med det perorala läkemedlet fingolimod jämfört med intravenös behandling med natalizumab vid MS. Arbetet utformades som en litteraturstudie där sökningar gjordes i PubMed genom Linnéuniversitetets bibliotek. De sökord som användes var "multiple sclerosis AND drug therapy AND fingolimod" samt "multiple sclerosis AND drug therapy AND natalizumab". Sökningarna ledde till att 7 studier granskades. Studierna visade att både fingolimod och natalizumab ger bättre effekt än placebo och de har dessutom bra säkerhet. Det var dock inga stora skillnader mellan de två substanserna. Vad gällde risken för progredierande funktionsnedsättning och risken för allvarliga biverkningar tycktes fingolimod vara något mera fördelaktigt, medan natalizumab hade en liten fördel vad gällde antalet gadoliniumförstärkta lesioner. Då man i några av fingolimodstudierna inte använde sig av intention-to-treat (ITT) och dubbelblindning kan läkemedlets effekter i dessa studier framstå som bättre än vad de är och de små förbättringar i effekter som sågs i resultaten blir osäkra. För att säkert kunna säga om det är någon skillnad i effekt och säkerhet mellan preparaten vore det önskvärt med nya dubbelblindade långtidsstudier av fingolimod där ITT använts vid analysen. Det vore också intressant med en randomiserad klinisk prövning som jämför fingolimod med natalizumab. De resultat som framförallt bör studeras är skovfrekvens, risk för ökande funktionsnedsättning och risk för allvarliga biverkningar, då dessa parametrar borde vara av störst värde för patienterna.

  • 288.
    Gustafsson, Niklas
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Utveckling av grönsakskorv: Kartläggning av näringsrelaterade utmaningar med vegankost och förbättring av näringstäthet i korv baserad på grönsaker.2016Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [sv]

    Människor blir mer och mer medvetna om hur produktion och konsumtion av kött

    påverkar miljön och folkhälsan. Detta har gjort att vegetariska alternativ till kött blivit

    alltmer populära och att nya produkter i kategorin utvecklats. Ett företag som nappat på

    denna trend är Lindvalls Chark AB i Strömsnäsbruk. Företaget har sedan länge tillverkat

    vanlig korv men har nu börjat utveckla en korv som är helt baserad på grönsaker med

    veganer som målgrupp. Syftet med föreliggande arbete var att sammanställa

    information om de näringsrelaterade problemen som är associerade med en strikt

    vegankost. Vidare var syftet att utifrån informationen identifiera specifikt vilka

    vitaminer och mineraler som Lindvalls tilltänkta korv skulle, för att bättre passa

    målgruppen veganer. Syftet var även att identifiera i vilka råvaror som dessa vitaminer

    och mineraler återfinns och sedan att i praktiska försök testa hur de skulle fungera som

    ingredienser. Resultaten tyder på att sesamfrön och havregryn fungerar bra som

    ingredienser i det tilltänkta receptet, men i olika koncentrationer. Båda ingredienserna

    leder till en ökning av innehållet av järn, kalcium och zink jämfört med det erhållna

    prototyp-receptet.

  • 289.
    Gustafsson, Rose-Marie
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Kan utbildningens innehåll av fysisk aktivitet påverka subjektiv hälsa, nivå av fysisk aktivitet och syreupptagningsförmåga?: En utvärdering av Värnamo kommuns hälsoutbildning2016Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    Aims: To examine if sessions of physical activity in Värnamo Municipality health education has any effect on the participant´s subsequent activity level and subjective health, and if the participants oxygen uptake changed after the education and if so, can this be linked to the reduced absenteeism.

    Methods: A questionnaire to all individuals who have taken the course and who still work in any of the municipal administrations and a cycle ergometer test conducted by a small group of the participants of the education.

    Results: No correlation was seen between the year the education was conducted (and thus if physical activity was included practicaly in the education) and the subjective health. A statistical significant association could be seen between education year and if the participant fully or partially reached the recommendations for physical activity. No influence on oxygen uptake could be identified at group level between any of the three test sessions and no correlation could be seen with the reduced sick leave.

    Conclusion: The study could not show that the adding of physical activity to the education gives any effect to the participants subsequent activity level or subjective health. What the participants reduced sick leave depends on can not be determined from this study. The perceived health and physical activity, to the extent that these factors could be evaluated, and oxygen uptake does not seem to be the reason.

  • 290.
    Gustafsson, Åsa
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Kadmium och preeklampsi - finns det något samband? En litteraturstudie2018Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    Background: Cadmium (Cd) is a metallic element with well-known negative health effects that we are exposed to in our environment, largely through diet. Preeclampsia annually affects 3-7% of all pregnant women and is one of the most common causes of morbidity and mortality for the mother and a major cause of prematurity and fetal growth retardation.

    Purpose: The purpose of the study was to investigate whether there is any correlation between Cd and preeclampsia and, if so, what the connection may be.

    Method: This study is a literature review based on scientific articles summarized.

    Results: All seven articles show a correlation between Cd and preeclampsia. In experimental models on pregnant rats exposed to Cd, rats develop characteristics of preeclampsia including high blood pressure. In humans, significant association between preeclampsia and higher Cd levels are observed in blood, serum and amniotic fluid.

    Conclusion: The articles show that there is a correlation between Cd and preeclampsia, although it cannot be established that it is a direct causal link without further research.

  • 291.
    Gustavsson, Henriette
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Delade tabletter: Problematik med delning av tabletter och dess ekonomiska konsekvenser2019Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [sv]

    Bakgrund: Idag är det vanligt förekommande att kunder ordineras delade tabletter. Ca 10 % av alla ordinationer är på delad tablett. För många innebär det problem då ålder, sjukdomar och tablettens utformning försvårar själva delandet. Kostnader diskuteras flitigt då flera studier förespråkar delad tablett för att sänka de ständigt ökande samhällskostnaderna för läkemedel.

    Syfte: Syftet var att undersöka den ekonomiska aspekten av delade tabletter, med tanke på de problem och risker det innebär.

    Metod:En enkätstudie gjordes med frågor rörande problem runt delning av tabletter, hur kunden informerats och hur den delade tabletthalvan förvarades. En gemensamt sammanställd databas utgjorde grunden för de beräkningar runt de kostnader som gjordes för delade tabletter.

    Resultat: I studien ingick 185 respondenter som ordinerats delad tablett. Av dessa upplevde 20 % problem med att dela en tablett. 52 % av deltagarna var personer över 71 år. 98 st ordinationer ingick i beräkningarna för en eventuell ekonomisk vinst/förlust med tablettdelning. Att dela tabletter i stället för att förskriva tabletter med halva substansmängden gav en merkostnad för dessa 98 ordinerade läkemedel på 2 031 kr. Detta pga. att apoteken bara får expediera läkemedel för tre månaders förbrukning, inom ramen för läkemedelsförmånen. Mindre förpackningar är per tablett dyrare än större.   En vinst på ca 23 000 kr, vilket motsvarar 40 %, skulle vara möjlig om tabletter med halva substansmängden förskrevs i förpackningsstorlekar för sex månaders förbrukning.  Här beräknades kostnaderna utifrån att läkemedlet såldes utan förmån. 

    Slutsats: Att dela tabletter utgör en risk då det ofta är svårt att dela tabletten i likvärdiga doser. Delade tabletter är inte ekonomiskt försvarbart inom läkemedelsförmånen för 65 % av ordinationerna enligt denna studie. I de fall läkemedlet finns som hel tablett i rätt styrka är det att rekommendera före att dela tabletter.

  • 292.
    Gustavsson, Maja
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Blodsocker- och insulinrespons efter intag av rågextrakt2014Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
  • 293.
    Göransson, Ulf
    et al.
    Uppsala University.
    Gunasekera, Sunithi
    Uppsala university.
    Malik, Sohaib
    Uppsala university.
    Park, Sungkyu
    Uppsala university.
    Slazak, Blazej
    Uppsala university.
    Jacobsson, Erik
    Uppsala University.
    Andersson, Håkan S.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Strömstedt, Adam
    Uppsala university.
    Peptide biodiscovery from plants and animals: structure to function2016In: Planta Medica, ISSN 0032-0943, E-ISSN 1439-0221, Vol. 82, no Supplement 1, article id SL49Article in journal (Other academic)
  • 294.
    Göransson, Ulf
    et al.
    Uppsala University.
    Jacobsson, Erik
    Uppsala University.
    Strand, Malin
    Swedish University of Agricultural Sciences.
    Andersson, Håkan S.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    The toxins of nemertean worms2019In: Toxins, ISSN 2072-6651, E-ISSN 2072-6651, Vol. 11, no 2, p. 1-36, article id 120Article in journal (Refereed)
    Abstract [en]

    Most ribbon worms (phylum: Nemertea) are found in marine environments, where they act as predators and scavengers. They are characterized by an eversible proboscis that is used to hunt for prey and thick mucus covering their skin. Both proboscis and epidermal mucus mediate toxicity to predators and preys. Research into the chemical nature of the substances that render toxicity has not been extensive, but it has nevertheless led to the identification of several compounds of potential medicinal use or for application in biotechnology. This review provides a complete account of the current status of research into nemertean toxins.

  • 295.
    Götesson, Åsa
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Cykloserins och ceftazidim/avibaktams effekt på multiresistenta gramnegativa bakterier2018Independent thesis Basic level (professional degree), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    Multiresistant gramnegative bacteria (MRGN) like Escherichia coli and Pseudomonas aeruginosa, constitute a global health issue. Due to the resistance development among bacteria, new options for treatment are needed. Extended Spectrum β-Lactamase (ESBL) is common among MRGN, and there are different types of ESBLs (as ESBLand ESBLCARBA). The increasing lack of treatment alternatives is mutual for the different ESBLs. The purpose of this study was to examine cycloserine and ceftazidime with the β-lactamase-inhibitor avibactam, two potentially new options for treatments effective against MRGN. To examine the minimum inhibitory concentration (MIC) for cycloserine (CYK) against E. coli (n=26) a in-house broth microdilution-method was used. Using two commercial broth microdilution-methods, isolates of P. aeruginosa with and without carbapenemaseproduction (n=23) were examined regarding MIC for ceftazidime/avibactam (CZA). 

    Regarding CYK, the median MIC-value of the E. coli-strains was 32 mg/L (16 - 64 mg/L), which is around the epidemiological cut-off-value (32 mg/L) for Mycobacterium tuberculosisfor which CYK is being used as treatment. The median of the MIC-values for CZA was 8 mg/L (<1 - ≥8 mg/L) for all P. aeruginosa-strains and 40% (2/5) of the carbapenemaseproducing isolates were sensitive according to the clinical breakpoint (S≤8 mg/L). In summary, this study shows that CYK has MIC-values against non-ESBL- and ESBL-producing E. coli at the same level as other pathogens where CYK is being used. Further, CZA may have effect against the isolates with reduced susceptibility against meropenem and ESBLCARBA-producing P. aeruginosa, although the isolates need to be susceptibility-determined before treatment. 

  • 296.
    Götrick, Fanny
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Kan elektroniska påminnelser förbättra följsamheten till läkemedel hos patienter som långtidmedicineras?2018Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    Adherence to a treatment is when the patient follows the planned treatment. A lower adherence can be when the patient is not taking their medication on time or the correct dose, not renew their prescriptions or that the patient is not following the recommendations of the treatment affecting their health. It is not unusual that the adherence is 50 % or lower in patients with chronic conditions. This affects the result of the treatment and cost the society a lot of money. A low degree of adherence is not always something the patient chooses, it can be because of forgetfulness or ignorance about their disease and its treatment. Adverse effects and attitudes about the treatment are factors that can make the patient unwilling to take their medication as prescribed.

    Mobile phones and smartphones increase in popularity all over the world and they can be an opportunity to affect adherence in patients with chronic conditions. Reminders and information can easily be sent out to a lot of patient to a low cost.

    The aim of this study was to find out if electronic reminders could increase adherence to treatment. The 5 studies that were chosen for this study analyzed if only reminders could affect the adherence or if reminders with information about the treatment and the patient’s condition could affect adherence.

    The result show that only reminders doesn’t affect adherence in patients with tuberculosis but for patients with acute coronary syndrome are electronic reminders effective for increase adherence to treatment with drugs. Increased understanding for the sickness and its treatment can possibly increase the adherence. Therefore education through mobile phone and reminders can be a good option to increase adherence among patients with chronic diseases.

  • 297.
    Hadi, Maysaa
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Är ingefära lika effektivt som NSAID avseende smärtlindring hos kvinnor med primär dysmenorré?2019Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    Dysmenorrhea is one of the most common gynecological condition reported by women with an estimated prevalence of 67% to 90% around the world. The condition is divided into primary and secondary dysmenorrhea and is defined as painful menstrual cramping in the abdominal region in combination with nausea, vomiting, insomnia, fatigue and diarrhea. The cause of the pain in primary dysmenorrhea is believed to result from an excessive increase in prostaglandin synthesis in the endometrium during the ovulatory cycle, which further causes vasoconstriction of the blood vessels in the uterine and increased uterine muscle contractions. The decrease of blood supply will result in ischemia and therefore induce pain. The treatments for dysmenorrhea include prostaglandin synthesis inhibitors such as Non -Steroidal Anti -Inflammatory Drugs (NSAID). NSAIDs are used as the first line therapy for pain relief of primary dysmenorrhea. In addition, one fourth of the patients don’t experience an effect of the drugs and some women don’t prefer the usage because of the lack of benefit, the adverse side effects or due to cultural reasons thus left with alternative treatments. Alternative non-synthetic treatments, such as herbal drugs, with effectiveness and low toxicity have been of high interest. Ginger, which is a herbal compound, have been reported to have beneficial effects on primary dysmenorrhea by inhibiting the prostaglandin synthesis and subsequent decrease of the pain. The aim of this study was to compare the effectiveness of ginger with NSAID on pain management in primary dysmenorrhea. This study is a literature review where five randomized controlled trials has been evaluated and analyzed. Two of them compared the pain management between NSAID and ginger in primary dysmenorrhea, two studies compared the pain management between placebo and ginger in primary dysmenorrhea and one study compared the pain management between NSAID and placebo in primary dysmenorrhea. All the studies where collected from the database PubMed. Overall the result showed that ginger influences pain relief in primary dysmenorrhea. In the two studies that evaluated gingers effect with placebo, both of them indicated a statistically significant difference in pain reduction (p<0.05). The treatment with ginger resulted in a pain reduction around 61% in the first study respectively around 34% in the second. In the studies which compared NSAID with ginger, the highest reduction NSAID could achieve was 56.5% whereas ginger achieved 60.1%. However, there were no statistically significant reduction in pain between them (p>0.05). The conclusion is that ginger as well as NSAID are effective in relieving pain in women with primary dysmenorrhea. Although the effect of ginger has been observed, further studies are necessary to establish gingers efficacy for the treatment of primary dysmenorrhea. Furthermore, it’s suggested that in the future extend the studies of ginger by comparing with multiple NSAID, other herbal compounds and methods used for primary dysmenorrhea with larger number of patients.

  • 298.
    Hagblom, Danijela
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Utvecklingen av svensk läkemedelsreklam för receptbelagda och receptfria läkemedel: Perioden från sekelskiftet år 1900 till nutid2018Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    Advertising has always been a powerful tool for the pharmaceutical industry.

    The history of pharma marketing in Sweden dates to the beginning of the 20th century. That was the time of “miraculous” drugs that could, according to advertisements, treat any kind of disease. Back then, marketing activities didn´t imply more than using empty promises, which were in combination with an alluring illustration, placed in a newspaper or an attractive public place. Consequently, negative perceptions have been plaguing the pharmaceutical marketing from the very beginning.

    In the years to come, medico-marketing in Sweden was struggling to rebuild its image.

    Marketing activities got strictly regulated at the national level via numerous lawsrules or procedures. Many authorities have been established to control the market and provide guideline for socially responsible, honest, respectful and up-to-date pharma marketing. As the result, up to the end of the 20th century conditions in pharmaceutical industry in Sweden have radically changed.

    Frivolous marketing of pharmaceutical drugs is today a matter of the past. However, there are still examples where pharmaceutical companies are breaking the law and are being accused of inappropriate marketing of drugs or lack of transparency in reporting results from negative clinical trials. Those examples are the warning signs for authorities that there is still a lot of space for further regulation of the market.

    Following thesis has an aim to answer to the question: “ How did pharma marketing in Sweden develop in the period between the beginning of the 20th century until today?”.

    Methodology used in this thesis include a qualitative method literature review, which is a survey of important articles, books and other sources relevant to the research question. A review of litterature published in Swedish language in period between the beginning of 20th century and today, showed that development of medico-marketing in Sweden took place within three following categories: regulatory law, ethics and media marketing.

    Apart from the progress in the analysed fields, there is still space for improvement. Some proposals for rasing the quality of marketing activities in the pharmaceutical industry include following: control of marketing materials before publishing, increasing the fees for marketing that is inconssistent with the regulatory laws and move toward greater transparency for clinical trial data. 

  • 299.
    Hahlin, Emma
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Optimering av metod för upparbetning av Klebsiella pneumoniae från blododlingskultur inför flödescytometriassisterad resistensbestämning2019Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [sv]

    Under vissa omständigheter kan bakterier kan ta sig in i blodbanan där de kan orsaka allvarliga infektioner (bakteriemi). Metoden som används för identifiering och resistensbestämning av bakterier i blododlingar kräver minst 16 timmars inkubation. Fram tills en resistensbestämning utförts kan empirisk antibiotikabehandling användas, men med ökande resistensutbredning blir det alltmer osäkert om denna behandling är verksam. Nyligen har en lappdiffusionsmetod för resistensbestämning direkt från blododling validerats, som kan läsas av efter 4, 6 och/eller 8 timmars inkubation. Det finns även publicerade arbeten där flödescytometriassisterad resistensbestämning används, men då krävs att bakterierna finns i tillräckligt hög koncentration, befinner sig i tillväxtfas och finns som renkultur. Syftet med examensarbetet var att optimera hantering av blododlingsflaskor så att bakterier från blododlingsflaskorna kunde isoleras med tillräcklig kvalitet och koncentration för att kunna utföra resistensbestämning med flödescytometri. Upprening av bakterierna utfördes med olika tvättbuffertar och sedan utfördes resistensbestämning med flödescytometri och  referensmetoden buljongspädning. Resultaten från uppreningen visade att sterilt vatten och Tween20 gynnade bakteriernas återhämtningsförmåga mest. Resistensbestämning utfördes med Klebsiella pneumoniae ATCC700603,  K. pneumoniae CCUG56233 och K. pneumoniae ATCC13882, som tvättats med sterilt vatten och Tween20. För CCUG56233 skiljde 1 spädningssteg i koncentrationsskalan mellan metoderna. ATCC-isolaten erhöll likartade MIC-värden (minimum inhibitory concentration) vid alla analyser men där fanns en skillnad på 2 spädningssteg mellan buljongspädning och analys med flödescytometri. Detta kan förklaras av skillnaden i inkubationstid mellan metoderna. Slutsatsen som kan dras är därför att resultaten från de två metoderna vid resistensbestämning är likartade och att sterilt vatten är mest lämpligt att använda vid upprening av bakterier. Fler undersökningar bör dock utföras.

  • 300.
    Halilovic, Muratka
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Kranskärlssjuka patienters attityd och följsamhet till läkemedelsbehandling: En kvantitativ undersökning om läkemedelsanvändning2015Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [sv]

    Brister i läkemedelsföljsamheten är ett världsomfattande problem. Varannan kroniskt sjuk patient följer inte sin läkemedelsordination. Trots starka bevis på att förebyggande behandlingar efter akut kranskärlssjukdom är effektiva har det i undersökningar visats att följsamheten till dessa mediciner är låg. Låg följsamhet leder till negativa hälsoeffekter; ökade hälso- och sjukvårdskostnader och ökad dödlighet. Syftet med denna studie var att undersöka attityder och följsamhet till läkemedel hos patienter med kranskärlssjukdom. Vidare skulle sambandet mellan olika faktorer hos patienterna och deras attityd och följsamhet till läkemedel undersökas.

    Studien baserades på enkätundersökningar och ingick som en delstudie i ett större forskningsprojekt ”God läkemedelsanvändning för äldre i Småland (GLAS)”. Till analysen samlades enkäter och journaluppgifter från totalt 91 kranskärlssjuka patienter. Enkäterna var BMQ-Specific (attityd till hjärtläkemedel) och MMAS-8 (följsamhet till kolesterolsänkande läkemedel). 

    Av 91 patienter som deltog var 75 % män. Medelåldern var 69 år (SD = 8,704 år) och genomsnittligt antal regelbundna läkemedel per patient var 7,2 (SD =2,419). En femtedel av patienterna hade stark oro om användningen av förskrivna hjärtläkemedel och 28 % hade bristande följsamhet till kolesterolsänkande läkemedel. De patienter som hade positiv attityd till sin medicin var också de som var mest följsamma.

    Slutsatser som kan dras av studien är att attityder till läkemedel är en viktig del i hur patienter väljer att följa eller inte följa sin behandlingsregim. Resultaten från studien kan komma att användas till att utveckla insatser för att förbättra patienters läkedelsföljsamhet och behandlingsresultat.

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