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  • 51.
    Andre, Ingemar
    et al.
    Lund University.
    Bjelic, Sinisa
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Computational assessment of folding energy landscapes in heterodimeric coiled coils2018In: Proteins: Structure, Function, and Bioinformatics, ISSN 0887-3585, E-ISSN 1097-0134, Vol. 86, no 7, p. 790-801Article in journal (Refereed)
    Abstract [en]

    The coiled coil structural motif consists of alpha helices supercoiling around each other to form staggered knobs-into-holes packing. Such structures are deceptively simple, especially as they often can be described with parametric equations, but are known to exist in various conformations. Even the simplest systems, consisting of 2 monomers, can assemble into a wide range of states. They can form canonical as well as noncanonical coiled coils, be parallel or antiparallel, where helices associate with different degrees of shift, tilt, and rotation. Here, we investigate the energy landscape of heterodimeric coiled coils by carrying out de novo folding simulations starting from amino acid sequence. We folded a diverse set of 22 heterodimers and demonstrate that the approach is capable of identifying the atomic details in the experimental structure in the majority of cases. Our methodology also enables exploration of alternative states that can be accessible in solution beyond the experimentally determined structure. For many systems, we observe folding energy landscapes with multiple energy minima and several isoenergetic states. By comparing coiled coils from single domains and those extracted from larger proteins, we find that standalone coiled coils have deeper energy wells at the experimentally determined conformation. By folding the competing homodimeric states in addition to the heterodimers, we observe that the structural specificity towards the heteromeric state is often small. Taken together, our results demonstrate that de novo folding simulations can be a powerful tool to characterize structural specificity of coiled coils when coupled to assessment of energy landscapes.

  • 52.
    Angeland, Malin
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Inverkan av n-3-fettsyror vid förlossningsdepression.2015Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [sv]

    n-3 fettsyror har en avgörande roll som komponent av plasmamembranets fosfolipider och tillhör gruppen fleromättade fettsyror. n- 3 fettsyrorna har en inverkan på cellstruktur och funktion och viktiga fettsyror är dokosahexaensyra (DHA) och eikosapentaensyra (EPA). DHA och EPA bildas från Alfalinolensyra (ALA) som är essentiell, det vill säga att den måste tillföras via kosten därför att kroppen inte kan tillverka den själv. ALA måste därför tillföras antingen genom fisk-och skaldjursintag och då framförallt fet fisk eller genom kosttillskott. EPA och DHA finns främst i hjärnan som till 60 % består av fett.

    Förlossningsdepression är en åkomma som drabbar ungefär 10-20 % av barnafödande kvinnor. Det är en komplex åkomma som kan bero på olika miljöfaktorer, genetiska anlag men kan även bero på kosten. Förlossningsdepression kan bli allvarligt både för modern och för barnet.

    Syftet med den här studien var att genom vetenskapliga artiklar undersöka om n-3 fettsyror kan ha en inverkan vid förlossningsdepression och isåfall genom vilka mekanismer. Det finns idag inget konkret svar på om n-3 fettsyror kan hjälpa vid förlossningsdepression samtidigt som många studier inom området har gjorts. Denna studie hade därför som syfte att eventuellt kunna bidra med ytterligare kunskap om n-3 fettsyror och förlossningsdepression och om fettsyrorna verkligen hjälper.

    Resultaten från de sex artiklar i studien som undersöktes visade inte på någon tydlig koppling mellan halten av n-3 fettsyror och förlossningsdepression. I tre av de sex studierna kunde dock en liten effekt observeras. En studie visade också att en högre snarare än en lägre nivå av fettsyror kunde öka risken för depression. Det behövs fler studier inom området för att få ett konkret svar.

  • 53.
    Angviken, Åsa
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    SSRIs effekt och säkerhet hos barn och ungdomar2016Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [sv]

    Depression är den näst mest kostsamma sjukdomen för samhället efter hjärt-kärlsjukdom, främst på grund av långa sjukskrivningsperioder. Sjukdomen kan uppstå när som helst från sex månaders ålder, men prevalensen ökar med åldern. Det finns ett antal stressrelaterade faktorer som skulle kunna leda till depression, så som stor sorg, verbala eller fysiska övergrepp samt en svår barndom. Vad som orsakar sjukdomen är ännu inte helt känt, men det finns teorier att halterna av serotonin och noradrenalin är lägre hos deprimerade personer. Behandling som används är olika former av samtalsterapi, men även läkemedel så som selektiva serotoninåterupptagshämmare (SSRI). Det finns teorier som sammankopplar användandet av SSRI med självmord, framförallt hos personer ≤19 år. Syftet med detta litteraturarbete var att undersöka om SSRI preparat har någon effekt på depression hos barn och ungdomar och om de är säkra eller kan få allvarliga konsekvenser så som självmord. Sökningar i PubMed gjordes för att hitta relevanta artiklar. Fem av de åtta inkluderade studierna rapporterade olika effekter och säkerhet hos olika SSRI preparat bland barn och ungdomar, jämfört med placebo. Två andra studier undersökte förekomsten av suicidalitet till följd av läkemedlen. Den sista studien jämförde toxikologiska data från Rättsmedicinalverket med receptregistret på antidepressiva läkemedel från  Socialstyrelsen. Endast två av de fem studerade preparaten (fluoxetin och citalopram) hade en bättre effekt än placebo i hela populationen och ytterligare ett (sertralin) hade bättre effekt hos ungdomar. Det begicks inga självmord i studierna.    De studier som har granskats i detta arbete tyder på att olika SSRI preparat har olika bra effekt samt olika säkerhetsprofiler. Det sågs inget tydligt samband mellan behandlingen och självmord, men en något förhöjd risk för suicidalitet.     

  • 54.
    Aniansson, Rebecka
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Utvärdering av snabb resistensbestämning för Staphylococcus aureus och Streptococcus pneumoniae direkt från positiv blododlingsflaska2019Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    Bacteria in the bloodstream may cause sepsis, therefore early and correct treatment is important. Antibiotic resistance is an increasing problem and antimicrobial susceptibility testing (AST) is essential for the patients survival. In sepsis with diagnosis based on blood culture, at least two days are required for results from AST.

    Routine AST-method in Swedish microbiological laboratories is the disc diffusion method standardized by the European Committee on Antimicrobial Susceptibility Testing (EUCAST). In disc diffusion, bacteria are grown on agar plates and inhibition zones around paper disks with antibiotics are used to measure the antibiotic effect. The method requires bacterial colonies as source material and takes 16–20 hours. EUCAST has further developed the method for Rapid Antimicrobial Susceptibility Testing (RAST). RAST is performed directly from positive blood culture bottles and inhibition zones are measured at 4, 6 and 8 hours. The method uses different breakpoints for categorization at the different timepoints. The purpose of the study was to evaluate RAST for Staphylococcus aureus and Streptococcus pneumoniae by examining bacterial isolates inoculated into blood culture bottles. Zone diameters were measured, and results were compared with those of standardized disk diffusion. For S.aureus, at 4 hours 102/184 (55%) readings were categorizable, at 6 hours 164/184 (89%) and at 8 hours 174/184 (95%). A total of 7 error categorizations occurred, 5 of which were underestimation of clindamycin resistance at 4 hours. For S.pneumoniae at 4 hours, 74/80 (92%) readings were categorizable, at 6 hours 73/80 (91%) and at 8 hours 77/80 (96%). Resistance was overestimated at 21 zone measurements at 4 hours.. RAST showed good results for S.aureus after 6 hours. For S.pneumoniae, further studies are required but RAST may work after 6 hours for penicillin resistance assessment.

  • 55.
    Apostolou, Vasileios
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Identification of covalently labeled, non-catalytic residues in proteins using liquid chromatography–mass spectrometry techniques2018Independent thesis Advanced level (degree of Master (One Year)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    Protein inhibition by covalent modifications has been widely explored during the last decades. Despite the worries regarding the toxicity and suitability of irreversible covalent drug inhibitors, lately they have gained more and more attention in scientific community. Here we investigate covalent modifications of non-catalytic protein residues with small-molecules as the potential building blocks for future drug discovery. The intricacies of protein structure and the environment they exist in, usually complicate the understanding of the reactivity between the amino acids and compounds. In this study, we attempted to approach this subject from an analytical point of view. By applying recombinant DNA techniques, we expressed and purified proteins of interest; using liquid chromatography–mass spectrometry (LC–MS) we attempted to label a number of redesigned proteins with the ultimate goal to apply this to human protein kinases, few of which will be presented here. This may potentially assist in rationally target residues in proteins, ideally not ctalytic ones that can be covalently modified, which can serve in later drug design studies. Furthermore, it will optimistically lead us to new efforts in discovering alternative methods of cancer treatment. Ultimately, the combination of experimental techniques and computational models will broaden our knowledge of covalent modifications at allosteric positions in proteins.

  • 56.
    Archer, Trevor
    et al.
    University of Gothenburg.
    Lindahl, Mats
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Physical exercise to determine resilience: Hormesic processes arising from physiologic perturbation2019In: Journal of Public Health and General Medicine, Vol. 1, no 1, p. 1-10Article in journal (Refereed)
    Abstract [en]

    The propensity for regular and repeated physical exercise to induce and maintain ahormesic effect upon health parameters over a broad range of disorder conditions through the progression of resilience to neurodegenerative disorders, diabetes, stroke, sarcopenia, osteopenia, immunosenescence, and metabolic syndrome has been examined. Beyond the alleviation fragility, fatigue, stress-distress and selective vulnerability perturbations induced by different forms of physical exercise may induce hormesis and/or autophagy, through the disruption of homeostasis and manifestation of adaptive responses, to instigate multi-layered resilience. The hormesis challenges, accomplished through daily exercise, the promotion of resilience at molecular, cellular, tissue, e.g. muscle, and organ, e.g. brain, immune-functioning, bone material, physiological and behaviour-expressive levels, have been observed both from pathophysiological and etiogenetic dimensions. Regular exercise over extended periods (optimally years and decades, preferably lifelong) is expected to shift the inverted-U shaped hormesis curve to the right thereby conferred resistance to disease and ill-being and ensuring strength and health advantages. It seems likely that chronic, regular exercise, consisting of suitable proportions of endurance and resistance type, performed daily over months, years or decades ought to instigate some manner of ‘behavioural sensitization’ whereby the health benefits of equivalent levels of exercise escalate incrementally.

  • 57.
    Arczykowska, Edyta
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Effekter av probiotika vid hypolaktasi och laktosintolerans2019Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [sv]

    Bakgrund: Laktos maldigestion är ett vanligt förekommande tillstånd hos mer än 75 procent av den vuxna befolkningen runt om i världen. Hypolaktasi innebär en minskad laktosnedbrytning på grund av en otillräcklig mängd av enzymet laktas. Laktosintolerans känneteckas av gastrointestinala symtom efter intag av laktosinnehållande produkt. Probiotika definieras som levande bakteriekultur och andra mikroorganismer, som i adekvata mängder har en hälsosam effekt hos en värd. Probiotika utgör en del av människans bakterieflora och har i flera studier uppvisat positiva egenskaper på människans mag-tarmhälsa och immunsystem. Syfte: Föreliggande litteraturstudie utvärderar effekten av probiotika vid hypolaktasi och laktosintolerans. Metod: Arbetet inkluderar sju vetenskapliga artiklar som utvärderar effekten av probiotika hos laktosintoleranta individer. Artiklarna erhölls från databasen Pubmed och sökningarna gjordes mellan september 2018 och februari 2019. Resultat: En sammanställning av studiernas resultat har visat på varierande grader av probiotikas effektivitet. I samtliga studier användes probiotika som ett enda behandlingsalternativ av laktos maldigestion. Metoden som användes vid bestämning av graden av intolerans i studierna, var ett laktosbelastningstest följt av utandningstest som är de vanligaste metoderna vid diagnostisering av hypolaktasi  och laktosintolerans. Probiotiska stammar som användes i försöken var olika stammar från Lactobacillus- (L. acidophilus, L. reuteri) och Bifidobakteriefamiljen (B. longum, B. animalis). I fyra av sju studier uppvisade probiotika en statistiskt säkerställd skillnad hos någon eller några av variabler som studerades. En minskning av vätekoncentrationen i utandningsluften efter probiotika tillskott kunde påvisas i tre granskade studierna. En minskning av gastrointestinala symtom så som diarré och flatulens registrerades i fyra av sju studier. Slutsats: En positiv relation har kunnat påvisas mellan probiotiska stammar och hypolaktasi. Regelbundet intag av produkter berikade med probiotika, kan minska symtom så som diarré och flatulens hos laktosintoleranta patienter. Det finns dock fortfarande för lite kunskap kring ämnet för att kunna rekommendera probiotika som ett enda behandlingsalternativ vid hypolaktasi. Det krävs mer forskning med fokus på de specifika probiotiska stammarna, dess ursprung och den adekvata dosen. Probiotika bör dock utan tvekan rekommenderas som ett komplement till behandlingen med enzymet laktas.

  • 58.
    Areda, Martha
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    The role of omega-3 fatty acids in the treatment of schizophrenia through modification of membrane phospholipids2016Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    Ever since the emergence of the hypothesis that linked the aetiology of schizophrenia with abnormal membrane phospholipids composition, an increasing number of evidences have suggested reduced membrane polyunsaturated fatty acids in patients with schizophrenia. This has led to a conduct of several studies to evaluate the efficacy of omega-3 fatty acid supplement in the modification of membrane phospholipids and treatment of schizophrenia. The two main omega-3 fatty acid classes, EPA and DHA, play a vital role in membranes. This project work reviews omega-3 fatty acid studies and summarizes their outcomes. Eight original articles (nine studies) were reviewed. Six out of nine studies measured RBC membrane fatty acids levels and all six studies reported a significant increase in EPA after EPA supplement. Two studies reported increased DHA post omega-3 fatty acid and DHA supplement, respectively. One study observed a dose-dependent increment in DHA after EPA supplement. Improved symptoms were observed in seven studies, while one study found a worsening of symptoms in patients with low baseline PUFA. Moreover, out of the six studies that evaluated the correlation between symptom change and membrane fatty acids change, three studies observed a correlation between increased EPA and symptom improvement. One study reported an increased AA associated with improved symptoms, in contrast to another study, which found a correlation between increased AA and worsened symptoms. The conclusion from this project work is that EPA supplement can increase the EPA levels in membranes; however, its therapeutic effect in schizophrenia requires further investigation using larger studies.

  • 59.
    Arildsson, Mathilda
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Har ketamin effekt mot terapiresistent depression?2019Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    Depression is a syndrome characterized by depressed mood, loss of interest and energy, feelings of guilt or worthlessness and thoughts of death and suicide. Over 300 million people suffer from depression and it is one of the leading causes of disability in the world.

    Today’s treatment for depression includes psychological treatment as well as pharmacological treatment. While there are many antidepressant drugs, it can take up to weeks or even months before a clinical effect in the severity of the depression can be noticed. In addition, one third of the patients do not achieve remission. These patients, after treatment with two antidepressant medications given at adequate doses for an adequate duration, are considered to have treatment-resistant depression (TRD).

    Ketamine is a drug long used for its anesthetic and analgesic effects, but it is also known as a party-drug that can cause out-of-body experience. However, it has also been found that a single-dose ketamine may give people with TRD a rapid antidepressant effect, within 24 hours. In contrast to current antidepressant medications which primarily acts on the monoaminergic system, ketamine instead acts on the glutamatergic system.

    The aim of this study was to evaluate if ketamine has an effect on people suffering from TRD.

    This study is a literature review where five randomized controlled trials on the effect of ketamine in patients with TRD have been analyzed. Four studies evaluated the effect of intravenous ketamine where one of them used a varied dose frequency and one of them used esketamine in various doses. The fifth study evaluated the effect of intranasal administration of ketamine. All studies were found in the database PubMed.

    The overall result shows that ketamine has an effect on TRD. After 24 hours all the studies showed a significant improvement in the severity of the depression with ketamine treatment compared to placebo (p <0.05). Ketamine treatment resulted in a 7-16 points larger reduction in depressive symptoms on the scales used compared to placebo. This represents on average a change from severe/moderately severe depression to mild depression. There was also a significant difference in response (at least 50 % reduction in points from baseline on the scale used) after 24 hours with ketamine treatment compared to placebo (p <0.05). The proportion of ketamine treated patients with response varied between 44-71 % compared to 0-6 % for placebo and 28 % for active placebo (midazolam).

    Even though ketamine seems to have an effect on patients with TRD there is still limited knowledge of how the antidepressant effect shall be maintained and the safety of long-term use. Further studies are needed to determine if ketamine will be an option in future antidepressant treatment against TRD.

  • 60.
    Arndt, Corinna
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Försäljning och förskrivning av antidepressiva läkemedel ur genusperspektiv.2017Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    In Sweden as well as in other countries women are consuming more health care and medicinal drugs than men. Partly, this difference can be explained by disease panorama and prescription of contraceptive pills. Biological and sociological factors may have an influence in cases of depression and GAD. Also, gender bias, a twisted view and prejudice concerning gender or sex, is thought to play a part. Among adults the depression prevalence rate ranges from 5% to 8%, and it increases to around 13% among elderly people. The lifetime risk of being effected by GAD is around 8% and the one-year prevalence rate ranges from 1.6% to 3.1%.

    The purpose of this study is to examine the sale/prescription of antidepressants from a gender perspective. Who prescribes the drugs? Are some drugs preferred to others, and are there geographical, age-related or economical differences between the sexes regarding prescriptions of antidepressants?

    Information about the type and the extent of the sale of antidepressants has been obtained from The National Board of Health and Welfare and The Medicine Unit (Läkemedelsenheten) in Kronoberg County.

    In 2015 more then 900.000 people bought antidepressants in Sweden. In Kronoberg (G County) 18.700 people bought antidepressants, 12.9% of them were women and 6.8% men. The sale in G County is slightly higher than in the rest of the country. The purchase among women increases relatively more than among men until menopause, after which the difference in purchase is stabilized. Almost 40% of the women and one of every four men purchase antidepressants in the highest ages. Counting in terms of DDD, women in G County are buying 1.87 times bigger volumes of antidepressants than men, of which 70% are prescribed at health centers, 14% in the mental health care area and the rest mainly by doctors working at hospitals. A small geographical difference can be seen between the counties in Sweden (+/- 5%). Within each county the prescription difference between men and women is small. Two drugs, sertraline (29%) and citalopram (19%), make up about half the volume. In the mental health care area slightly larger volumes of venlafaxine and duloxetine are prescribed to women compared to men. Men are prescribed somewhat more of fluoxetin. Relatively more women (65%) are treated for depression in primary care than in psychiatric care (59%). In primary care, women are prescribed relatively more Duloxetine. No difference in cost (pharmacy sales price (PSP)) per DDD can be observed between the sexes.

    Conclusion: Approx. 10% of the Swedish population bought antidepressants in 2015. Two times more women than men are purchase antidepressants. There is no definite answer to what is causing this difference. Can it be caused by overconsumption among women, or inadequate treatment among men? The greater part of antidepressants is prescribed in out-patient care, which indicates that antidepressants are used mainly in cases of less noticeable anxiety symptoms and mild to moderate depression. According to The Swedish Board of Health and Welfare these cases should foremost be treated with CBT.

  • 61.
    Asif, Sana
    et al.
    Uppsala University, Sweden.
    Asawa, Kenta
    Univ Tokyo, Japan.
    Inoue, Yuuki
    Univ Tokyo, Japan.
    Ishihara, Kazuhiko
    Univ Tokyo, Japan.
    Lindell, Björn
    Uppsala University, Sweden.
    Holmgren, Robin
    Uppsala University, Sweden.
    Nilsson, Bo
    Uppsala University, Sweden.
    Ryden, Anneli
    Swedish University of Agricultural Sciences, Sweden.
    Jensen-Waern, Marianne
    Swedish University of Agricultural Sciences, Sweden.
    Teramura, Yuji
    Uppsala University, Sweden;Univ Tokyo, Japan.
    Nilsson Ekdahl, Kristina
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences. Uppsala University, Sweden.
    Validation of an MPC Polymer Coating to Attenuate Surface-Induced Crosstalk between the Complement and Coagulation Systems in Whole Blood in In Vitro and In Vivo Models2019In: Macromolecular Bioscience, ISSN 1616-5187, E-ISSN 1616-5195, Vol. 19, no 5, article id 1800485Article in journal (Refereed)
    Abstract [en]

    Artificial surfaces that come into contact with blood induce an immediate activation of the cascade systems of the blood, leading to a thrombotic and/or inflammatory response that can eventually cause damage to the biomaterial or the patient, or to both. Heparin coating has been used to improve hemocompatibility, and another approach is 2-methacryloyloxyethyl phosphorylcholine (MPC)-based polymer coatings. Here, the aim is to evaluate the hemocompatibility of MPC polymer coating by studying the interactions with coagulation and complement systems using human blood in vitro model and pig in vivo model. The stability of the coatings is investigated in vitro and MPC polymer-coated catheters are tested in vivo by insertion into the external jugular vein of pigs to monitor the catheters' antithrombotic properties. There is no significant activation of platelets or of the coagulation and complement systems in the MPC polymer-coated one, which was superior in hemocompatibility to non-coated matrix surfaces. The protective effect of the MPC polymer coat does not decline after incubation in human plasma for up to 2 weeks. With MPC polymer-coated catheters, it is possible to easily draw blood from pig for 4 days in contrast to the case for non-coated catheters, in which substantial clotting is seen.

  • 62.
    Asif, Sana
    et al.
    Uppsala University.
    Jonsson, Nina
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences. Uppsala University.
    Teramura, Yuji
    Univ Tokyo, Japan.
    Gustafson, Elisabet
    Univ Uppsala Hosp.
    Nilsson Ekdahl, Kristina
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences. Uppsala University.
    Nilsson, Bo
    Uppsala University.
    Conjugation of human recombinant CD39 to primary human hepatocytes protects against thromboinflammation2015In: Xenotransplantation, ISSN 0908-665X, E-ISSN 1399-3089, Vol. 22, p. S87-S87Article in journal (Other academic)
  • 63.
    Asif, Sana
    et al.
    Uppsala University.
    Nilsson Ekdahl, Kristina
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences. Uppsala University.
    Fromell, Karin
    Uppsala University.
    Gustafson, Elisabet
    Uppsala University Hospital.
    Barbu, Andreea
    Uppsala University.
    Le Blanc, Katarina
    Karolinska Institutet;Karolinska University Hospital.
    Nilsson, Bo
    Uppsala University.
    Teramura, Yuji
    Uppsala University;The University of Tokyo, Japan.
    Heparinization of cell surfaces with short peptide-conjugated PEG-lipid regulates thromboinflammation in transplantation of human MSCs and hepatocytes2016In: Acta Biomaterialia, ISSN 1742-7061, E-ISSN 1878-7568, Vol. 35, p. 194-205Article in journal (Refereed)
    Abstract [en]

    Infusion of therapeutic cells into humans is associated with immune responses, including thromboinflammation, which result in a large loss of transplanted cells\ To address these problems, heparinization of the cell surfaces was achieved by a cell-surface modification technique using polyethylene glycol conjugated phospholipid (PEG-lipid) derivatives. A short heparin-binding peptide was conjugated to the PEG-lipid for immobilization of heparin conjugates on the surface of human mesenchymal stem cells (hMSCs) and human hepatocytes. Here three kinds of heparin-binding peptides were used for immobilizing heparin conjugates and examined for the antithrombogenic effects on the cell surface. The heparinized cells were incubated in human whole blood to evaluate their hemocompatibility by measuring blood parameters such as platelet count, coagulation markers, complement markers, and Factor Xa activity. We found that one of the heparin-binding peptides did not show cytotoxicity after the immobilization with heparin conjugates. The degree of binding of the heparin conjugates on the cell surface (analyzed by flow cytometer) depended on the ratio of the active peptide to control peptide. For both human MSCs and hepatocytes in whole-blood experiments, no platelet aggregation was seen in the heparin conjugate-immobilized cell group vs. the controls (non-coated cells or control peptide). Also, the levels of thrombin-antithrombin complex (TAT), C3a, and sC5b-9 were significantly lower than those of the controls, indicating a lower activation of coagulation and complement. Factor Xa analysis indicated that the heparin conjugate was still active on the cell surface at 24 h post-coating. It is possible to immobilize heparin conjugates onto hMSC and human hepatocyte surfaces and thereby protect the cell surfaces from damaging thromboinflammation. Statement of Signigficance We present a promising approach to enhance the biocompatibility of therapeutic cells. Here we used short peptide-conjugated PEG-lipid for cell surface modification and heparin conjugates for the coating of human hepatocytes and MSCs. We screened the short peptides to find higher affinity for heparinization of cell surface and performed hemocompatibility assay of heparinized human hepatocytes and human MSCs in human whole blood. Using heparin-binding peptide with higher affinity, not only coagulation activation but also complement activation was significantly suppressed. Thus, it was possible to protect human hepatocytes and human MSCs from the attack of thromboinflammatory activation, which can contribute to the improvement graft survival. (C) 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  • 64.
    Ataei, Shakila
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Optimering av analysmetoden hos koldioxid-isotop-analysatorn, Picarro-G2131-i2015Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    Marine bacteria are microscopically visible organisms that can survive in most of the marine environments. Their function is to decompose dead organic matter, and thus contribute to the carbon cycle in the oceans. They utilizes dissolved organic matter in the oceans and produce carbon dioxide through respiration. This carbon dioxide can be measured with modern instruments to determine the primary production of the ecosystem and determine what carbon sources are responsible for the energy flow in the ecosystem. During this study, the possibility, advisability and the sensitivity of measuring bacterial respiration with the carbon dioxide isotope analyzer Picarro-G2131-i was examined. Further, the method was developed. For the experiment, two species of proteorhodopsin containing marine bacteria Polaribacter sp. strain MED152 and Dokdonia sp. strain MED134 were used. Growth and respiration of the bacteria were studied in nutrient rich medium. To test the Picarro-instrument is sensitivity, the respiration of both bacterial species was performed in respectively dilution series. In addition, the growth and respiration of MED134 in nutrient-poor conditions in light and darkness condition was compared. To study the impact of light on the growth of bacteria. No significant difference was found between MED134´s growth and respiration in light and dark. The method could be improved by modification such as changing pump, shorten tubes, remove a safety bottle and use a refefence bottle.

     

    Conclusion

    The carbon dioxide isotope analyzer Picarro-G2131-i is a sensitive instrument and can detect both the 12CO2 and 13CO2. According to the growth experiment, the bacteria grow very rapidly in nutrient rich medium. For comparing bacterial growth in light and dark, the correct light intensity and sufficient nutrient must be used.

  • 65.
    Ataei, Tahereh
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Förekomst av penicillinkänslighet hos blododlingsisolat av Staphylococcus aureus2014Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    Staphylococcus aureus is the most clinically important Staphylococcus species and is associated with high mortality in patients with positive blood cultures. S. aureus bacteria may cause a variety of disease manifestations ranging from minor skin infections to life-threatening conditions such as pneumonia, meningitis, osteomyelitis, endocarditis, toxic shock syndrome (TSS) and sepsis. This microorganism belonging to the gram positive cocci may also be part of the normal flora. In Sweden, penicillinase-stable penicillins are the primary alternatives to treat S. aureus infection. Mutations in genes encoding the penicillin binding proteins (PBP2) in the bacteria which lead to a lower affinity for the  beta-lactam antibiotics define  methicillin resistant S. aureus (MRSA) which is a significant global health problem. Other resistance mechanisms of S. aureus are present, and one of these is penicillinase production which is associated with resistance to penicillin G. In order to detect penicillinase production in S. aureus, there are several methods but the European guidelines recommend disc diffusion and the clover-leaf test for follow-up if the zone diameter for benzylpenicillin (PcG) is 26 mm or more. There are no modern Swedish studies on the prevalence of S. aureus susceptible to PcG and this has recently attained interest from infectious disease physicans. Thus, the purpose of this study was to investigate the frequency of S. aureus susceptible to PcG from blood cultures isolated during 2012 from the Kalmar county.    Disc diffusion testing showed that 32% of 90 unique isolates tested had an inhibition zone diameter of PcG that was ≥ 26 mm in diameter. All of these isolates were confirmed as PcG sensitive with clover-leaf test. Internal controls showed little variation and external control isolates showed full agreement with the results obtained from a Danish study, suggesting that PcG zone diameter of ≥ 26 mm in combination with cloverleaf test can be used to detect penicillin susceptibility of S. aureus.    In conclusion, this study shows that nearly 1 /3 of the blood culture isolates of S. aureus from Kalmar are sensitive to benzylpenicillin.

  • 66. Aveyard,, J
    et al.
    Hajne, J.
    Månsson, Alf
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Persson, Malin
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    van Delft,, F.C.M.J.M.
    van Zijl, J.
    Snijder, J.
    van den Heuvel,, F.C.
    Nicolau,, D.V.
    Actin motility confinement on micro/nanostructured surfaces.2013In: Proc. SPI 8587, Imaging, Manipulation, and Analysis of Biomolecules, Cells, and Tissues XI, 858722 (February 22, 2013) / [ed] Daniel L. Farkas; Dan V. Nicolau; Robert C. Leif, SPIE - International Society for Optical Engineering, 2013, p. 858722-858727Conference paper (Refereed)
  • 67.
    Azuma, Tomoyuki
    et al.
    Univ Tokyo, Japan.
    Matsushita, Taishi
    Univ Tokyo, Japan.
    Manivel, Vivek Anand
    Uppsala University, Sweden.
    Nilsson Ekdahl, Kristina
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences. Uppsala University, Sweden.
    Nilsson, Bo
    Uppsala University, Sweden.
    Teramura, Yuji
    Univ Tokyo, Japan;Uppsala University, Sweden.
    Takai, Madoka
    Univ Tokyo, Japan.
    Poly(2-aminoethyl methacrylate)-based polyampholyte brush surface with carboxylic groups to improve blood compatibility2020In: Journal of Biomaterials Science. Polymer Edition, ISSN 0920-5063, E-ISSN 1568-5624, p. 1-15Article in journal (Refereed)
    Abstract [en]

    Zwitterionic material-based polymer brush significantly prevents protein adsorption and cell adhesion, which leads to the blood compatibility. However, zwitterionic polymer itself is difficult to be modified further, for the blood compatibility since the charged balance is impaired after the modification. In this research, chemically modifiable mixed charge polymer brush is designed, without impairing its characteristics. Condensed mixed charge polymer brush will work like zwitterionic material because neighbouring opposite charge is reported to be important in the zwitterionic material. Cationic polymer brush with primary amine group, which is based on 2-aminoethyl methacrylate (AEMA), was prepared and modified by succinic anhydride to obtain carboxylic group induced poly(AEMA). The ratio of primary amine group and carboxylic group was optimized to obtain the polyampholyte brush. The blood compatibility was evaluated by measuring coagulation/complement activation, protein adsorption and cell adhesion induced by the polymer. Our designed cationic-based polyampholyte brush prevented coagulation/complement activation comparable to poly(2-methacryloyloxyethyl phosphorylcholine) brush, based on intra-monomer interaction, because condensed mix charge works like zwitterion.

  • 68.
    Bacovic, Betim
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Validering och tillämpning av en bioassay baserad på Artemia salina för undersökning av giftverkan: Experimentell studie2019Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    Background: Alpha-nemertides are about 30 aminoacids long so-called ICK peptides, which have been shown to be very toxic to shore crabs and a number of other invertebrates. A survey project where the presence of alpha-nematides in marine so-called ribbon worms has been investigated for four years as a collaboration between researchers at the Linnaeus University, Uppsala University, the Swedish Agricultural University and the University of Queensland, Brisbane. The nature and toxicity of these peptides have been investigated by several methods, including a bioassay based on Artemia salina, for which a method previously has been developed. The task of this work was to test the method in order to be able to use it in a quality-assured way in the laboratory at Linnaeus University.

    Aim/Method: The aim of this study was to develop and validate a reliable protocol for estimating acute toxicity in shore crabs using juveniles from Artemia Salina (brine shrimp) in microtiter plates.

    Results:  Results showed that the artemia assay was reliable. Results between the series A1, B1 and C1 showed the same IC50. The emetin studies showed, compared to previous studies, a devation of about a ten-potency, however, EC50 for alpha-1 and alpha-2 matched previous studies from Uppsala.

    Discussion/Conclusion: Assay can be used for comparison with corresponding trials in Uppsala. Further attempts are necessary to clarify within which timeframes to check the microwell plates. 

  • 69.
    Baftijaj, Jehon
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Etniska skillnader i läkemedelsrespons för substanser relevanta vid hjärt-kärlsjukdomar2017Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    There are many factors that play a role in the response of a drug. An interesting factor that is often discussed in the academia is the role of ethnicity. Differences in the expression of CYP enzyme, protein transporters and receptors between different ethnic groups believed to affect the outcome of many drugs relevant to cardiovascular disease. Polymorphism is believed to play an important role in this regard. Genetic alleles that differ through ethnicity-based polymorphism causes CYP enzymes and protein transporters to respond differently to different drugs. It is nevertheless not always fully explored if these ethnic differences are always due to genetic or non-genetic causes.

    There are however important changes toward the notion of recognizing ethnicity as a key role in pharmaceutical development. The Food and Drug Administration in the US have for example released guidance on how to define and work towards categorizing ethnicity in clinical research. There are also several western countries creating guidelines for drug therapy specific to ethnic groups.

    The purpose of this literary work was to study the differences between ethnic groups in terms of dosing, efficacy and pharmacokinetics of drugs used in cardiovascular disease.

    Five studies were used in the literary work. The first study examined the differences in dosing for warfarin therapy between different ethnicities. The second trial studied the plasma exposure of rosuvastatin between Caucasian and Asian people. The third study examined the effect of the ACE inhibitor enalapril in black and white patients with left ventricular dysfunction. The fourth study investigated the effect of beta blocker atenolol in white and black participants. The last study was done to compare the effect of the thiazide diuretic chlorthalidone against calcium channel inhibitors and ACE inhibitors in black and non-black patients.

     

    The results showed that warfarin dosage differs between ethnicities. Plasma exposure of rosuvastatin is different between Caucasian and Asian people. ACE inhibitors work better with white patients, atenolol is more effective for white patients and chlorthalidone works better in black patients with certain cardiovascular diseases.

     

    The studies presented indicate that there are differences in drug response in various ethnicities and these distinctions are different in extent and significance. It can be argued for genetic and non-genetic causes of differences depending on the drug being studied. 

  • 70.
    Bahari, Hajar
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Har valproat och fenytoin negativa effekter på bentäthet hos människa?2018Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    Background: Epilepsy is a chronic neurological disease characterized by at least two repeated, unprovoked seizures. During a seizure, a discharge occurs in the brain's nerve cells resulting in overactivation of nerve cells. Epilepsy is usually treated with anti-epileptics. Antiepileptics may have a negative effect on bone density. The degree of bone loss varies between different antiepileptics.

    Objective: The purpose of this study was to critically evaluate relevant clinical studies to answer the question of what effects valproate (a non-EIAEDs) and phenytoin (an EIAED) have on bone density in humans.

    Methods: This literature study evaluated seven scientific studies that were found in the PubMed database. Selected studies investigated the effect of valproate and phenytoin on bone mineral density in epileptic patients.

    Results: A total of seven studies are reported which include 296 adult patients with epilepsy, three of which were investigated by the effect of phenytoin and six valproate on bone density. Outcome values indicated in T-score or Z-score. BMD was measured in the lumbar and thigh neck area of five of a total of six studies with valproate and three studies showed a decreased BMD in LS and FN after treatment with valproate. BMD was reduced in hip and hip bone in two and one study and in the valproate group respectively. Two out of three phenytoin studies showed a decreased BMD in LS. All three phenytoin studies showed a reduced BMD in the UN. BMD was lowered in hip line in a phenytoin group study.

    Conclusions: In summary, this literature study shows that phenytoin (non-EIAED) and valproate (EIAED) have adverse effects on bone density. BMD was reduced by 75% in the LS and UN regions of the valproate group and decreased in LS and the UN in the phenytoin group 85% and 100% respectively. BMD in the hip joint of the VPA group was reduced by 27% and decreased by 83% in the PHT group. Patients with phenytoin showed higher bone loss than the valproate group despite having a low dose of drug during treatment and patients in the valproate group received high doses of the drug. According to the result, the rate of bone loss loss increases with the duration of treatment times, patients in the phenytoin group had longer treatment times compared to valproate and showed more BMD reduction.

  • 71.
    Bardage, Carola
    et al.
    Med Prod Agcy, Uppsala / Uppsala Univ.
    Ekedahl, Anders
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences. Med Prod Agcy, Uppsala.
    Ring, Lena
    Med Prod Agcy, Uppsala / Uppsala Univ.
    Health-Care Professionals' Perspectives on Multi-Dose Dispensed Medicines2013In: Pharmacoepidemiology and Drug Safety, ISSN 1053-8569, E-ISSN 1099-1557, Vol. 22, p. 251-251Article in journal (Other academic)
  • 72.
    Barzanji, Tara
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Kan användning av paracetamol under graviditeten medföra risk för barnet och leda till beteendeproblem?2018Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    Introduction: Paracetamol is the most common medicine used as painkiller in the world. Since it has been on the market for a very long time it has been thought to be one of the safest medicines to use during pregnancy. Many women use this medicine for different indications during pregnancy thinking it is safe for the fetus. However, the mechanism of action for paracetamol is still unknown and therefore there is no information about how it could affect the fetus.

    Objective: To study paracetamol safety during pregnancy and its effect on the fetus and behaviour in childhood.

    Method: The information search for this literature study has been done through searching for different articles in the database pubmed. In these articles, pregnant women who used paracetamol during pregnancy have been analysed to see the effect on their children.

    Result: Different articles used in this literature study have shown an association between prenatal paracetamol exposure and behavioural problems in children. One study shows that if paracetamol is used during pregnancy the risk increases to get a Hyperkinetic disorder, HKD diagnosis (Hazard ratio (HR)= 1,37; 95% confidence interval (CI), 1,19-1,59), similarly the risk to get an ADHD-diagnosis increases (HR=1,29: 95% CI, 1,15-1,44).

    Discussion: The association between prenatal paracetamol exposure and behavioural problems has been shown in different studies made om pregnant women even though the exact mechanism is still unknown. Changes in children’s epigenetics seem to be associated with prenatal paracetamol exposure. Changes in DNA-methylation of genes previously linked to ADHD have been detected.  

    Conclusion: Prenatal paracetamol exposure seems to be associated with child behavioural problems. Therefore, paracetamol may not be a completely safe medicine in pregnancy and all pregnant women should have this information available to avoid unnecessary use especially during the second and third trimester.

  • 73.
    Becconi, Olga
    et al.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences. University of Cagliari, Italy.
    Ahlstrand, Emma
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Salis, Andrea
    University of Cagliari, Italy.
    Friedman, Ran
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Protein-ion Interactions: Simulations of Bovine Serum Albumin in Physiological Solutions of NaCl, KCl and LiCl2017In: Israel Journal of Chemistry, ISSN 0021-2148, Vol. 57, no 5, p. 403-412Article in journal (Refereed)
    Abstract [en]

    Specific interactions that depend on the nature of electrolytes are observed when proteins and other molecules are studied by potentiometric, spectroscopic and theoretical methods at high salt concentrations. More recently, it became clear that such interactions may also be observed in solutions that can be described by the Debye-Hückel theory, i.e., at physiological (0.1 mol dm−3) and lower concentrations. We carried out molecular dynamics simulations of bovine serum albumin in physiological solutions at T=300 and 350 K. Analysis of the simulations revealed some differences between LiCl solutions and those of NaCl and KCl. The binding of Li+ ions to the protein was associated with a negative free energy of interaction whereas much fewer Na+ and K+ ions were associated with the protein surface. Interestingly, unlike other proteins BSA does not show a preference to Na+ over K+. Quantum chemical calculations identified a significant contribution from polarisation to the hydration of Li+ and (to a lesser degree) Na+, which may indicate that polarisable force-fields will provide more accurate results for such systems.

  • 74.
    Behailu Bekele, Haimanot
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Atypisk aktivering av komplementprotein C52019Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
  • 75.
    Bengtsson, Elina
    et al.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Persson, Malin
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Kumar, Saroj
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Månsson, Alf
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Actomyosin Interactions and Different Structural States of Actin Filaments2013In: Biophysical Journal, ISSN 0006-3495, E-ISSN 1542-0086, Vol. 104, no 2, p. 480A-481AArticle in journal (Other academic)
  • 76.
    Bengtsson, Elina
    et al.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Persson, Malin
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Kumar, Saroj
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Månsson, Alf
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Altered Structural State of Actin Filaments Upon MYOSIN II Binding2015In: Biophysical Journal, ISSN 0006-3495, E-ISSN 1542-0086, Vol. 108, no 2 Supplement 1, p. 299A-300A, article id 1499-PosArticle in journal (Other academic)
  • 77.
    Bengtsson, Elina
    et al.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Persson, Malin
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Månsson, Alf
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Analysis of Flexural Rigidity of Actin Filaments Propelled by Surface Adsorbed Myosin Motors2013In: Cytoskeleton, ISSN 1949-3584, Vol. 70, no 11, p. 718-728Article in journal (Refereed)
    Abstract [en]

    Actin filaments are central components of the cytoskeleton and the contractile machinery of muscle. The filaments are known to exist in a range of conformational states presumably with different flexural rigidity and thereby different persistence lengths. Our results analyze the approaches proposed previously to measure the persistence length from the statistics of the winding paths of actin filaments that are propelled by surface-adsorbed myosin motor fragments in the in vitro motility assay. Our results suggest that the persistence length of heavy meromyosin propelled actin filaments can be estimated with high accuracy and reproducibility using this approach provided that: (1) the in vitro motility assay experiments are designed to prevent bias in filament sliding directions, (2) at least 200 independent filament paths are studied, (3) the ratio between the sliding distance between measurements and the camera pixel-size is between 4 and 12, (4) the sliding distances between measurements is less than 50% of the expected persistence length, and (5) an appropriate cut-off value is chosen to exclude abrupt large angular changes in sliding direction that are complications, e.g., due to the presence of rigor heads. If the above precautions are taken the described method should be a useful routine part of in vitro motility assays thus expanding the amount of information to be gained from these. (c) 2013 Wiley Periodicals, Inc.

  • 78.
    Bengtsson, Elina
    et al.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Persson, Malin
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences. Karolinska Institutet ; McGill Univ, Canada.
    Rahman, Mohammad A.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Kumar, Saroj
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences. Delhi Technol Univ, India.
    Takatsuki, Hideyo
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Månsson, Alf
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Myosin-Induced Gliding Patterns at Varied [MgATP] Unveil a Dynamic Actin Filament2016In: Biophysical Journal, ISSN 0006-3495, E-ISSN 1542-0086, Vol. 111, no 7, p. 1465-1477Article in journal (Refereed)
    Abstract [en]

    Actin filaments have key roles in cell motility but are generally claimed to be passive interaction partners in actin-myosin -based motion generation. Here, we present evidence against this static view based on an altered myosin-induced actin filament gliding pattern in an in vitro motility assay at varied [MgATP]. The statistics that characterize the degree of meandering of the actin filament paths suggest that for [MgATP] >= 0.25 mM, the flexural rigidity of heavy meromyosin (HMM)-propelled actin filaments is similar (without phalloidin) or slightly lower (with phalloidin) than that of HMM-free filaments observed in solution without surface tethering. When [MgATP] was reduced to <= 0.1 mM, the actin filament paths in the in vitro motility assay became appreciably more winding in both the presence and absence of phalloidin. This effect of lowered [MgATP] was qualitatively different from that seen when HMM was mixed with ATP-insensitive, N-ethylmaleimide-treated HMM (NEM-HMM; 25-30%). In particular, the addition of NEM-HMM increased a non-Gaussian tail in the path curvature distribution as well as the number of events in which different parts of an actin filament followed different paths. These effects were the opposite of those observed with reduced [MgATP]. Theoretical modeling suggests a 30-40% lowered flexural rigidity of the actin filaments at [MgATP] <= 0.1 mM and local bending of the filament front upon each myosin head attachment. Overall, the results fit with appreciable structural changes in the actin filament during actomyosin-based motion generation, and modulation of the actin filament mechanical properties by the dominating chemomechanical actomyosin state.

  • 79.
    Bengtsson Lager, Benita
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Är Multipel kemisk känslighet associerat med inflammatorisk respons?2018Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [sv]

    Redan under 1880-talet beskrevs i USA symtom som liknar de som idag relateras till multipel kemisk känslighet (MCS). MCS innebär en överkänslighet för väldigt låga doser av ett okänt antal kemikalier som finns i vår omgivning. Det är en icke allergisk kronisk störning som karaktäriseras av ospecifika symtom (en akut hypersensitivitet) kopplade till exponering av vanligt förekommande flyktiga kemikalier, exempelvis från parfymerade produkter, tobaksrök och nytryckta tidningar och magasin. Det finns indikationer på att inflammation är en bakomliggande orsak till hypersensitiviteten hos patientgruppen med MCS. Syftet med denna litteraturstudie var att redogöra för symtom och bakomliggande mekanismer kopplade till MCS, och se huruvida det finns grund att tro att inflammation bidrar till sjukdomsutveckling. Information har insamlats både från böcker och vetenskapliga artiklar. I många studier beskrivs symtom hos MCS-patienter som liknar symtomen vid infektionssjukdomar (trötthet, mjukvävnadsmärta, koncentrationssvårigheter), och andra symtom som påminner om astma. Vissa MCSpatienters astmaliknande symtom har även kunnat lindrats av antihistaminer, nässpray med kortikosteroider eller utspädda lokalanestetika. Det finns även en symtombild som kan associeras med inflammation. Med förbättrade vetenskapliga studier är det troligt att det i framtiden går att få fram en mer exakt inflammatorisk profil. Detta skulle kunna bidra till en ökad förståelse om några av de bakomliggande mekanismerna för vissa av symtomen hos denna patientgrupp.

  • 80.
    Bengtsson, Marie
    et al.
    Department of Plant Protection Biology, Swedish University of Agricultural Sciences, Alnarp, Sweden.
    Boutitie, Anne
    SUAMME, Mas de Saporta, Lattes, France.
    Jósvai, Julia
    Plant Protection Institute MTA ATK, Budapest, Hungary.
    Toth, Miklos
    Plant Protection Institute MTA ATK, Budapest, Hungary.
    Andreadis, Stefanos
    Department of Plant Protection Biology, Swedish University of Agricultural Sciences, Alnarp, Sweden.
    Rauscher, Stefan
    Swiss Federal Research Station, Wädenswil, Switzerland.
    Unelius, C. Rikard
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Witzgall, Peter
    Department of Plant Protection Biology, Swedish University of Agricultural Sciences, Alnarp, Sweden.
    Pheromone races of Cydia splendana (Lepidoptera, Tortricidae) overlap in host plant association and geographic distribution2014In: Frontiers in Ecology and Evolution, E-ISSN 2296-701X, Vol. 2, p. Article ID: 46-Article in journal (Refereed)
    Abstract [en]

    Identification of the sex pheromone of Cydia splendana (Lepidoptera, Tortricidae) bypheromone gland analysis followed by field trapping with synthetic compounds showsthe occurrence of two pheromone races. Acorn moth females from Sweden, whereoak Quercus robur is the only host plant, use a blend of the E,Z and E,E isomers of8,10-dodecadien-1-yl acetate. In Central and Southern Europe, where C. splendana feedson chestnut Castanea sativa and several species of oak, males respond to another isomerblend, E,E and Z,E. The distribution of the two pheromone races of C. splendana overlapsin Northern France, where they share oak as plant host. Differences in sex communicationsignals between these populations of C. splendana corroborate the role of specific materecognition in speciation events.

  • 81.
    Bergecliff, Terese
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Viscosity and Acid Stability in Low-fat Mayonnaise with Varying Proportions of Xanthan Gum and Guar Gum2016Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    Mayonnaise is a mixture of egg yolk, vinegar, water, spices and 70-80% oil forming a semi-solid oil-in-water emulsion. When preparing a low-fat mayonnaise with an increased water content, thickening agents are required for increased viscosity and emulsion stability. The hydrocolloids xanthan gum and guar gum are sometimes used for this purpose and they act synergistically creating a viscosity increase. However, guar gum has poor acid stability, and because mayonnaise is an acidic product guar gum will eventually start to degrade causing a viscosity decrease and subsequent emulsion separation. Despite this fact, guar gum and xanthan gum are extensively used in mayonnaises today.

    The aim of this degree project was to explore how the synergy between guar gum and xanthan gum influences the viscosity of a low fat mayonnaise and whether high acidity will have an impact on the viscosity over a 4-week period. This was to examine if and if so, how a mayonnaise recipe can be modified to maintain a cost efficient product with the desired rheological properties in times of hydrocolloid price fluctuations. The study was conducted by preparing 15 mayonnaises with 50% fat, either at pH 3,5; 4 or 5 and a total of 0,6 % hydrocolloids with varying proportions of guar gum and xanthan gum. The mayonnaise samples were studied by measurements of viscosity, color changes and a visual comparison of their mayonnaise-like flow-properties compared to Hellmann’s Real Mayonnaise used as reference.

    The viscosity of the mayonnaises increased with increasing ratio of guar gum. On the other side, there were greater viscosity losses in mayonnaises with increasing ratio of guar gum 4 weeks after preparation compared to 4 days, with no apparent signs of correlation between higher acidity and hydrocolloid degradation. Mayonnaises with 20% xanthan gum and 80% guar gum had the texture most similar to the reference. In these low-fat mayonnaises, the use of more xanthan gum led to an undesired “slimy” texture and a lower viscosity – an important aspect if adjusting a low-fat mayonnaise recipe by increasing the ratio of xanthan gum. Because a commercial mayonnaise sometimes is consumed several months after manufacturing, that time frame is most likely required in order to fully measure how much the high acidity in mayonnaise will affect its viscosity. This project has shown a pattern where viscosity in the assessed mayonnaises starts to decrease a few weeks after preparation. However to find out exactly to what extent and how this would affect the overall product, and ultimately: if guar gum/xanthan gum combinations are suitable for long-term mayonnaise applications, further studies are required. 

  • 82.
    Berggren, Sofia
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Water holding capacity and viscosity of ingredients from oats: the effect of b-glucan and starch content, particle size, pH and temperature2018Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    Oats is a crop that contains a high amount of fiber, protein and fat, but like all other crops it contains mostly starch. In this study the focus has been oat flours and brans with different b-glucan content. The health benefits of b-glucan, a soluble fiber are well documented and a correlation between intake of b-glucan with high molecular weight and a low glycemic response has been observed. Food with a low glycemic index can lower the risk for diseases like type 2 diabetes, cardiovascular diseases and obesity. Also a connection between intake of b-glucan with high molecular weight and a reduction of LDL-cholesterol has been observed. b-glucans from oat absorb water and build a viscous gel, which make them an interesting component when developing new products, as a fat replacer in for example meat products and pastries. To optimize the use of flours and brans with a modified b-glucan content in new applications, the water absorption was measured with a method called Solvent Retention Capacity and the viscosity with a Rapid Viscosity Analyzer (RVA). The results showed that a higher amount of b-glucan in the flour or bran, a higher water holding capacity (WHC) was observed. The WHC for oat flour with a b-glucan content at 2% was calculated to 73±7%, while the WHC for oat bran with a b-glucan content at 28%, was calculated to a WHC of 880±45%. A comparison of different flours and brans indicates that dietary fiber, where b-glucan have the greatest impact on the WHC. The result from the RVA indicates that a flour with a combination of a high b-glucan content (0.24g) and high starch content (3.72g) leads to a high viscosity 12700 cP, compared to other flours or brans with either a lower b-glucan content (0.12g) or lower starch content (0.12g) gives lower final viscosity, 5390 and 780 cP. The result also indicates that other factors such as a smaller particle size and a higher temperature during the heating step (95°C instead of 64°C) might give a higher viscosity. 

  • 83.
    Bergman, Anna
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Har förskrivningen av antibiotika till våra vanligaste husdjur, hund och katt förändrats från 2009 till 2014 och i så fall, hur?2015Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [sv]

    Baserat på en rapport från e-hälsomyndigheten tillsammans med allmänt tillgänglig material från Statens Veterinärmedicinska Anstalt och Statens Jordbruksverk fastslås att expedieringen av antimikrobiella medel till hund och katt i Sverige har minskat med c:a 27 % mellan 2009 och 2014. Största delen av de antimikrobiellamedlen förskrivs till hund (70 %). Den mesta använda gruppen av antimikrobiella medel till båda djurslagenär penicilliner. Därefter vanligast använda grupper av antimikrobiella medel till hund är linkosamider,övriga antibakteriella betalaktamer och antibakteriella kinolonderivat. Till katt används näst penicillinerfrämst antibakteriella kinolonderivat och linkosamider. Samma grupper dominerar år efter år men förskrivningenav de enskilda medlen varierar inom respektive grupp. Minskningen är mer framträdande gällandehund och ses främst för cefalexin, enrofloxacin och klindamycin. De senaste åren ses, för bådadjurslagen enviss ökning i användningen av kombinationer med sulfametoxazol och trimetoprim. Mellan 6 och 7 % av dentotala mängden läkemedel till hund och katt utgörs av humanläkemedel. Baserat på de dokument som sammanställtsi detta arbete tycks det som att svenska veterinärer tar sitt ansvar och bidrar till den minskandeanvändningen av antimikrobiella medel i samhället. Med fortsatt medveten och kontrollerad användning av antimikrobiella medel till djur kommer Sverige att kunna fortsätta att föregå som gott exempel och som en förebild för övriga Europa och kanske även för resten av världen.

  • 84.
    Bergman, I. M.
    et al.
    Aarhus Univ.
    Edman, Kjell
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    van As, P.
    Res & Technol Ctr, Technol & Serv BV, Hendrix Genet Res, Boxmeer, Netherlands.
    Huisman, A.
    Res & Technol Ctr, Technol & Serv BV, Hendrix Genet Res, Boxmeer, Netherlands.
    Juul-Madsen, Helle Risdahl
    Aarhus Univ.
    A two-nucleotide deletion renders the mannose-binding lectin 2 (MBL2) gene nonfunctional in Danish Landrace and Duroc pigs2014In: Immunogenetics, ISSN 0093-7711, E-ISSN 1432-1211, Vol. 66, no 3, p. 171-184Article in journal (Refereed)
    Abstract [en]

    The mannose-binding lectins (MBLs) are central components of innate immunity, facilitating phagocytosis and inducing the lectin activation pathway of the complement system. Previously, it has been found that certain single-nucleotide polymorphisms (SNPs) in porcine MBL1 and MBL2 (pMBL1, pMBL2) affect mRNA expression, serum concentration, and susceptibility to disease, but the combinatory effect of pMBL1 and pMBL2 genotypes needs further elucidation. In the present study, pMBL1 and pMBL2 alleles, combined pMBL haplotypes, and MBL-A concentration in serum were analyzed in purebred Landrace (N = 30) and Duroc (N = 10) pigs. Furthermore, the combined pMBL haplotypes of 89 PiStrain x (Large White x Landrace) crossbred pigs were studied, and the genotypes of 67 crossbreds challenged with Escherichia coli were compared to their individual disease records. In the purebred animals, three non-synonymous SNPs and a two-nucleotide deletion were detected in the coding sequence of pMBL2. The two-nucleotide deletion was present at a frequency of 0.88 in the Landrace pigs and 0.90 in the Duroc pigs, respectively. In the crossbreds, the T allele of the SNP G949T in pMBL1-previously shown to have profound effect on MBL-A concentration even in the heterozygote condition-was detected in 47 % of the animals. Finally, an association was found between low-producing MBL genotypes and low body weight on the day of weaning in the same animals.

  • 85.
    Bergman, I. M.
    et al.
    Aarhus Univ, Denmark.
    Okumura, N.
    Inst Soc Technoinnovat Agr Forestry & Fisheries, Japan.
    Uenishi, H.
    Natl Inst Agrobiol Sci, Japan.
    Hammer, S. E.
    Univ Vet Med Vienna, Austria.
    Knoll, A.
    Mendel Univ Brno, Czech Republic.
    Edfors, Inger
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Juul-Madsen, H. R.
    Aarhus Univ, Denmark.
    Wild boars from Sweden, Austria, the Czech Republic and Japan possess intact mannose-binding lectin 2 (MBL2) genes2015In: International Journal of Immunogenetics, ISSN 1744-3121, E-ISSN 1744-313X, Vol. 42, no 3, p. 204-207Article in journal (Refereed)
    Abstract [en]

    The two-nucleotide deletion recently detected in the mannose-binding lectin 2 gene in purebred and crossbred domestic pigs was not found among 68 wild boars representing 4 populations from Europe and Asia. This suggests that the deletion is a result of breeding and/or genetic drift/bottle necks.

  • 86.
    Bergman, Ingrid-Maria
    et al.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences. Aarhus University, Denmark.
    Sandholm, Kerstin
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Nilsson Ekdahl, Kristina
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences. Uppsala university.
    Okumura, Naohiko
    Institute of Society for Techno-innovation of Agriculture, Japan.
    Uenishi, Hirohide
    National Institute of Agrobiological Sciences, Japan.
    Guldbrandtsen, Bernt
    Aarhus University, Denmark.
    Essler, Sabine
    Univ of Veterinary Medicine, Austria.
    Knoll, Ales
    Mendel University, Czech Republic.
    Heegaard, Peter
    Technical University of Denmark, Denmark.
    Edfors, Inger
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Juul-Madsen, Helle
    Aarhus University, Denmark.
    MBL1 genotypes in wild boar populations from Sweden, Austria, the Czech Republic and Japan2013In: International Journal of Immunogenetics, ISSN 1744-3121, E-ISSN 1744-313X, Vol. 40, no 2, p. 131-139Article in journal (Refereed)
    Abstract [en]

    The single nucleotide polymorphism (SNP) G949T in the mannose-binding lectin (MBL) 1 gene has been associated with low MBL-A concentration in serum and detected at different frequencies in various European pig populations. However, the origin of this SNP is not known. Part of the MBL1 gene was sequenced in 12 wild boar/Large White crossbred pigs from the second backcross (BC 2) generation in a family material originating from two wild boar x Large White intercrosses. Also, MBL-A serum concentration was measured in the entire BC 2 generation (n = 45). Furthermore, the genotypes of 68 wild boars from Sweden, Austria, the Czech Republic, and Japan were determined in regard to five previously described SNPs in MBL1. The T allele of G949T was present among the BC 2 animals. MBL-A serum concentration in the BC 2 animals showed a bimodal distribution, with one-third of the animals at levels between 0.7 and 1.6 μg mL−1 and the remaining pigs at levels around 13 μg mL−1. There was a co-variation between the presence of the T allele and low MBL-A concentration in serum. The genotyping of the wild boars revealed differences between populations. The T allele of G949T was not detected in the Austrian and Japanese samples and is thus unlikely to be an original feature of wild boars. In contrast, it was present at high frequency (0.35) among the Swedish wild boars, probably representing a founder effect. Five MBL1 haplotypes were resolved. Only two of these were present among the Japanese wild boars compared to four in each of the European populations. This difference may reflect differences in selection pressure and population history.

  • 87.
    Bergsell, Philip
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Karakterisering av mikroalger och återvinning av biprodukter2018Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
  • 88.
    Bergström, Maria
    et al.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Ganji, Suresh
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Naidu Veluru, Ramesh
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Unelius, C. Rikard
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    N-Iodosuccinimide (NIS) in Direct Aromatic Iodination2017In: European Journal of Organic Chemistry, ISSN 1434-193X, E-ISSN 1099-0690, no 22, p. 3234-3239Article in journal (Refereed)
    Abstract [en]

    N-Iodosuccinimide (NIS) in pure trifluoroacetic acid (TFA) offers a time-efficient and general method for the iodination of a wide range of mono-and disubstituted benzenes at room temperature, as demonstrated in this paper. The starting materials were generally converted into mono-iodinated products in less than 16 hours at room temperature, without byproducts. A few deactivated substrates needed addition of sulfuric acid to increase the reaction rate. Another exception was methoxybenzenes that preferentially were iodinated by NIS in acetonitrile with only catalytic amounts of TFA.

  • 89.
    Berkeby Banérsson, Emilia
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Hållbarhetsstudier och granskning av automatvalidering av analysresultat vid analys av prostataspecifikt antigen Hållbarhetsstudier och granskning av automatvalidering av analysresultat vid analys av prostataspecifikt antigen2013Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [sv]

    Prostatacancer är den vanligaste orsaken till cancerdöd hos män i Sverige. Cirka 9500 patienter får diagnosen prostatacancer varje år. Prostatacancer diagnostiseras med hjälp av analys av tumörmarkören prostataspecifikt antigen (PSA) i plasma.

    Syftet med den aktuella studien var att undersöka den preanalytiska stabiliteten av PSA i plasma och att undersöka hur förändrade provtagningsanvisningar och provtagningsrutiner påverkade analysresultat, arbetsförhållanden och patientsäkerhet.

    Analysmetoden som användes vid studien var electrochemiluminiscence immunoassay (ECLIA), vilken nyttjar ljus för detektion av antigen-/antikroppskomplex.

    I en första studie visades att centrifugerade PSA-prover med icke avhälld plasma, förvarade i 6o C, kan analyseras upp till 5 dagar efter provtagning. Detta till skillnad från nuvarande metodbeskrivning som kräver avhälld plasma vid analys 24 timmar efter provtagning. En andra studie visade att PSA-prov, förvarat i 6o C, centrifugerat och analyserat 24 timmar efter provtagning gav oförändrade PSA-värden jämfört med PSA-prov som centrifugerats och analyserats direkt efter provtagning. Detta till skillnad från nuvarande metodbeskrivning där prov skall centrifugeras inom 2 timmar och att ocentrifugerat prov skall förvaras i rumstemperatur.

    Nya automatvalideringsgränser och införandet av laboratoriedataprogrammet Delta-check gav en halvering av antalet analysresultat som ej automatvalideras.

    Studien visar att PSA var mer stabilt än tidigare förmodats och att förändrade rutiner vid analys av PSA och införande av automatvalidering med Delta-check kan leda till ett förbättrat och mer effektivt arbete för personalen på laboratoriet och ge ökad patientsäkerhet.

  • 90.
    Bernestrå, Isadora
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Ebolaviruset - nu och då: varför har utbrottet 2013-2015 blivit så stort?2015Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [sv]

    Bakgrund: Ebola upptäcktes för första gången 1976 i ett dubbelt utbrott i Sudan och Zaire i Afrika. Det pågående utbrottet av ebola virus sjukdom (EVD) startade i Guinea 2013 och har sedan dess spridits vidare till Liberia, Sierra Leone, Nigeria, Mali och Senegal. T.o.m. 4 mars 2015 har nästan 24 000 smittats och 10 000 avlidit vilket är mer än 50 gånger fler än i det tidigare största utbrottet i Uganda 2000. Viruset består av fem arter: Bundibugyo, Reston, Sudan, Tai Forest och Zaire. Vektorn för viruset är fortfarande okänd men förmodas vara flygande hundar (fruit bats) som själva är resistenta. Symtomen innefattar bl.a. feber, trötthet, kräkning, diarré, ledsmärtor och mukosala blödningar. Behandlingen består vanligen av vätskeersättning. Det finns varken godkänt vaccin eller läkemedel i dagsläget men flertalet studier pågår för att utveckla bl.a. antikropparna ZMapp och antiviral behandling med Brincidofovir.

    Syfte: Redogöra för tidigare och pågående utbrott av ebola och undersöka vilka faktorer som bidragit till att epidemin 2013-2015 inträffat och fått stora proportioner i Västafrika.

    Metod: Till det aktuella ämnet har den senaste informationen inhämtats via WHO och CDCs respektive hemsidor mellan 23/2-9/3 2015.

    Resultat: En kombination av faktorer har bidragit till att det pågående utbrottet blivit större än tidigare. Länderna som drabbats har inte varit förberedda, virusarten ebola Zaire har hög dödlighet, sjukvård och infrastruktur är svag och kulturen är djupt grundad i ett samhälle där utbildningen är låg. Befolkningen behöver respekteras och utbildas för att de aktivt ska kunna vara delaktiga i att stoppa smittspridningen av viruset. Ju mindre geografisk yta viruset är fördelat på desto lättare blir det att kontrollera och bekämpa det.

    Diskussion: Guinea, Liberia och Sierra Leone har alla drabbats extra hårt av pågående EVD utbrott och behöver nu få hjälp med återuppbyggnad av ett fungerande sjukvårdssystem som befolkningen kan lita på och med personal som kan arbeta under säkra förhållanden. Stort fokus bör också läggas på att implementera kulturen i de skyddsåtgärder som behövs för att förhindra ytterligare spridning och framtida utbrott. Ytterligare forskning krävs för att kunna erbjuda bättre behandling och profylax.

  • 91.
    Berthelsen, Isabell
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Naturens Läkemedel: Harmin mot cancer?2016Independent thesis Basic level (university diploma), 180 HE creditsStudent thesis
    Abstract [sv]

    Harmine is a beta-carboline present in medical plants such as Peganum harmala that have been used traditionally as anticancer therapy. In this study, the aim was to examine if it really does have an effect on cancer and if so, mechanism of action. To do so several earlier studies on the subject have been examined. The result is promising but there is still a lot to study on the subject.

    Harmine really does inhibit tumour growth. It has been tested on both cellcultures and mice and has proven to decrease tumourgrowth significantly with little effect on normal cells. There have also been studies were harmine has been modified to be more efficient and less harmful. One way to make Harmine more effective is to put a 2-amino-2deoxy-D-glucose on the molecule. Since the cancer cell uses a lot of energy for its growth a big proportion of the medicine will end up here. Another way is to attach a methionin-group to it. This is also taken up exccessively by the cancer cells. Substitution in different areas may reduce it’s toxicity; Substitution with a formiat at R3 for example decreased its toxicity so that no side effects were seen in the mice in the study whereas harmine in large doses gave neurotoxic symptoms. Harmines antitumour activity seems to be due to several mechanisms of action. For example a higher level of p53 has been observed efter treatment with harmine. P53 has been called ”the guardian of the genome” because of its role in preventing genome mutation. In some studies a decrease in vascular endothelial growth factor (VEGF) has also been seen. This is an important factor for the growth of new vessels toward the tumour-site. A reduction in COX-2 has also been seen. Inhibition of COX-2, for example by NSAID, is associated with lower risk for coloncancer. A fourth possible mechanism of action could be a decrease or inhibtion of CDKs/Cyklins wich are necessary for the cellcycle-progression. Although a promising substance, there is still a lot to study. It would be interesting to se comparations to established drugs on the market and also what the long term side effects of Harmine could be. The studies so far have only been done under a short period of time, i.e., weeks or months.

  • 92.
    Beyer, Sarah
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Effekten av vitamin D2 vs. D3 på 25(OH)D-statusen: En litteraturstudie2018Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    Background: Vitamin D comes in two different forms, D3 from animals (cholecalciferol) and D2 from plants (ergocalciferol). There has been different opinions among physicians and the general public about which of the calciferols is more potent to raise 25(OH)D-levels in the blood, which is the value that is measured to determine the vitamin D-status in the body. Since vitamin D deficiency is common among the people of the Nordic countries it is important to know which form has the best effect and should be used to treat and prevent vitamin D deficiency. Furthermore, it is relevant for vegans who do not eat the animalic D3, where recommendations might have to be changed.

    Aim: The aim of the study was to find out if there were differences in potency of D2 vs. D3 to raise 25(OH)D status in the blood and if so, to find possible explanations for those differences.

    Methods: Six relevant original articles that examined the effect of D2 vs. D3 on 25(OH)D status in the blood, were found in the database PubMed. The studies where published between the years 2008 and 2017. The participants were healthy adults.

    Results: Four of the studies suggested that D3 is more effective than D2 in order to raise the 25(OH)D status. One study concluded that there is no difference in the effectiveness of D2 vs D3 and one study showed that D2 is more effective than D3 when it comes to daily treatment but that D3 has a better effect than D2 when treatment happens on a two or four weekly basis with large doses.

    Conclusion: Most of the articles suggested a better effectiveness of D3 than D2 to raise 25(OH)D levels in the blood. However, besides the mixed results, the number of studies and participants was too small to come to a clear conclusion.

  • 93.
    Biglarnia, Ali-Reza
    et al.
    Skåne University Hospital;Lund University.
    Huber-Lang, Markus
    Univ Hosp Ulm, Germany.
    Mohlin, Camilla
    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.
    The multifaceted role of complement in kidney transplantation2018In: Nature Reviews Nephrology, ISSN 1759-5061, E-ISSN 1759-507X, Vol. 14, no 12, p. 767-781Article, review/survey (Refereed)
    Abstract [en]

    Increasing evidence indicates an integral role for the complement system in the deleterious inflammatory reactions that occur during critical phases of the transplantation process, such as brain or cardiac death of the donor, surgical trauma, organ preservation and ischaemia-reperfusion injury, as well as in humoral and cellular immune responses to the allograft. Ischaemia is the most common cause of complement activation in kidney transplantation and in combination with reperfusion is a major cause of inflammation and graft damage. Complement also has a prominent role in antibody-mediated rejection (ABMR) owing to ABO and HL A incompatibility, which leads to devastating damage to the transplanted kidney. Emerging drugs and treatment modalities that inhibit complement activation at various stages in the complement cascade are being developed to ameliorate the damage caused by complement activation in transplantation. These promising new therapies have various potential applications at different stages in the process of transplantation, including inhibiting the destructive effects of ischaemia and/or reperfusion injury, treating ABMR, inducing accommodation and modulating the adaptive immune response.

  • 94.
    Bild, Filippa
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Utvärdering av BD Vacutainer® Rapid Serum Tube vid analys av S-Paracetamol och S-Etanol2014Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [sv]

    Avdelningen för klinisk kemi vid Länssjukhuset i Kalmar analyserar läkemedel och alkoholer med BD Vacutainer® Plus Plastic Serum Tube (Serum Tube), som kräver en koagulationstid i upp till 60 minuter. BD Vacutainer® Rapid Serum Tube (RST™) innehåller trombin och kräver en koagulationstid på endast 5 minuter. Syftet med studien var att undersöka möjligheten att förkorta den preanalytiska väntetiden före centrifugering vid intoxikationsanalyser i serumrör från akutmottagningen. Studien utfördes genom att jämföra RST™ med Serum Tube vid analys av S-Paracetamol och S-Etanol. Totalt analyserades 70 prover för S-Paracetamol, varav 35 RST™ och 35 Serum Tube från 35 patienter. Analys av S-Etanol utfördes på 60 prover, varav 30 RST™ och 30 Serum Tube från 30 patienter. RST™ centrifugerades efter 5 minuter och Serum Tube efter 50 minuter, före kolorimetrisk analys på analysinstrumentet VITROS® 5,1 FS. Resultaten för S-Paracetamol var inom intervallet 74,9 – 198,7 µmol/L för RST™ och inom 76,6 – 195,3 µmol/L för Serum Tube. Resultaten för S-Etanol var inom intervallet 7,5 – 74,5 mmol/L för RST™ och inom 7,5 – 74,8 mmol/L för Serum Tube. Pearsons korrelationskoefficient var 0,9977 för S-Paracetamol och 0,9980 för S-Etanol och det fanns en liten positiv bias vid analys med RST™ för båda analyterna, men ingen signifikant skillnad (p>0,05) mellan provrören påvisades. Användning av RST™ på akutmottagningen medför en förkortad preanalytisk väntetid och en snabbare turnaround time (TAT). Hypotesen att S-Paracetamol och S-Etanol kan analyseras med RST™ på VITROS® 5,1 FS stämmer, med undantag för höga koncentrationer av S-Paracetamol som inte kunde utvärderas. För att RST™ ska kunna användas rutinmässigt bör därför ytterligare studier utföras.

  • 95.
    Bjelic, Sinisa
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Protein carriers for passage of the Blood-Brain Barrier2015In: Protein Science, ISSN 0961-8368, E-ISSN 1469-896X, Vol. 24, p. 177-177Article in journal (Other academic)
  • 96.
    Bjenning, Lovisa
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Implementation of improved fat standardization using statistical process control2019Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    The aim of this project was to apply statistical process control (SPC) and measure the variation of fat content in milk in order to improve the standardization, so that the fat content does not change more than 0.03 percentage units from target. Recommendations of how to adjust the standardization should also be developed. The standardization takes place together with pasteurization in one of the three pasteurizers. Thereafter, the milk goes to a common product tank with all the pasteurizers. Samples from the three pasteurizers and the product tank were collected and analyzed on MilkoScan FT2 and the fat content was plotted into Shewhart and cumulative sum (CUSUM) charts. Sampling on the pasteurizers from startup showed that samples should be taken after about 20 minutes, because then the variation is in general smaller. The data from the product tank showed a smaller variation than the pasteurizers. Because the milk from all the pasteurizers is transported into one product tank, it is impossible to know which pasteurizer that is out of control and need to be adjusted. Therefore, the conclusion is that samples should be taken after the pasteurizer and plotted into Shewhart and CUSUM charts. Action limits were achieved from the Shewhart and CUSUM charts, respectively. These are the limits that should be used to determine when adjustments of the pasteurizers are needed, and not the brand limits that are considerably wider. If the measurements fall outside the second limit in the Shewhart chart (three times the standard deviation) or outside the limits (H) in the CUSUM chart, the standardization before the pasteurizer in question should be considered. It is not known if using SPC will improve the fat content to be within 0.03 percent units from target, because the recommendation has not been applied in the process yet, but it going to be that soon.

  • 97.
    Björk, Amanda
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Utvärdering av flödescytometrisk metod för antimikrobiell känslighetsbestämning: en jämförelse med konventionell buljongspädningsteknik2018Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
  • 98.
    Björk, Josefin
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Erytrocytinnehåll i plasmakomponenter: En jämförelse mellan teststickan Multistix, hematologiinstrumentet Advia 2120 och manuell räkning i mikroskop med Bürkers räknekammare2018Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    Following blood donation of 450 mL of whole blood from volunteer donors, the blood is separated into plasma, erythrocytes and thrombocytes. Controls are performed to investigate the separation performance. E.g. the plasma units are not allowed to contain more than 6x109 erythrocytes per liter. Whole blood does normally contain 4-6x1012 erythrocytes per liter. The primary indication for plasma transfusion is massive bleeding, a treatment mainly associated with risks such as transfusion related acute lung injury (TRALI) and transfusion associated circulatory overload (TACO). The aim of the thesis work was to find a decision limit for the determination of the erythrocyte content in plasma components produced prior to transfusion. The limit was to be determined by a comparison between the Multistix 8 SG test stick, Body fluid program in the Advia 2120 hematology instrument and manual count in the Bürker counting chamber. Analysis were performed on 38 samples, of which 18 samples were prepared by addition of extra erythrocytes to either exceed the control limit or find the transition point to the highest result level of the stick. The average and median of the quantitative results from the Bürker counting chamber for the 20 approved controls, broken down by the categories on the stick, were calculated. All results were between 0.063x109/L and 2.08x109/L. Of the 38 samples analyzed, 37 received a result <10x109/L on the Advia 2120. Based on these results, the decision limit at which a component control is guaranteed an approved result was determined to ≤2+ on the test stick. In the case of a 3+ result, a confirmatory quantitative analysis must be performed. The conclusion was that the test stick Multistix 8 SG could be used as a screening method for analyzing the erythrocyte content of the plasma components produced. The conclusion was also that the Adviaprogram used is not suitable for analysis of the erythrocyte content in plasma.

  • 99.
    Björnsson, Anna
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Helparasitvaccination mot malaria - status idag och utmaningar för framtiden2019Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    Background: Malaria is still one of the most common infectious diseases in the world and there is an overwhelming threat to the development of resistance to different control methods such as drugs and insecticides. A durable vaccine with sterile protection would reduce and maybe eradicate the disease. The most serious cases of malaria are caused by Plasmodium falciparum that is transmitted through the bites of infected Anopheles mosquitoes. The life cycle of malaria is extremely complex and different vaccine candidates have effects at different stages. Naturally acquired immunity develops gradually after many years of clinical episodes but never becomes sterile. RTS,S is the only vaccine candidate who has been in phase III clinical trials. Unfortunately this vaccine has limited efficacy, like many other subunit vaccines, due to rapidly diminishing antibody titers. Whole parasite vaccines have the ability to generate a greater quantity and breadth of antigenic exposure within both the humoral and cellular immunity. This results in stronger immune response and can provide sterile protection. The development of whole parasite vaccines has mainly focused on the pre-erythrocytic stage and the most tested vaccine candidates that are in early clinical trial are radiation-attenuated sporozoites (RAS), chemoprophylaxis and sporozoites (CPS) and genetically attenuated parasites (GAP).

    Aim: The purpose of this literature study is to examine and compare the vaccine efficacy and durability towards P. falciparum of the two whole parasite vaccine candidates: RAS and CPS and to examine the importance of dose and different routes of administration.

    Methods: Fourteen different clinical studies were selected from PubMed to be included in this literature study. Different variables were selected for study: the vaccine efficacy and it´s durability after controlled human malaria infection (CHMI) using P. falciparum parasites homologous or heterologous to the vaccine strain, the correlation between the immunogenicity and protection, the importance of the dose and different kinds of administration and vaccine safety.

    Results: According to the findings in the literature study, direct venous inoculation of RAS-vaccine and CPS-vaccine have the ability to give short and longlasting protection against CHMI using P. falciparum parasites homologous to the vaccine strain. The dose is of great importance to the vaccine efficacy and CPS-vaccine has the ability to give potent protection with much lower doses than RAS-vaccine. Some immune mechanisms in the blood correlate with protection but it seems to be the number of CD8+ T-cells in the liver that are of greatest importance for longlasting and steril protection. Whole parasite vaccines are safe but transient parasitemia is common when using CPS-vaccine. Unfortunately, vaccines with longlasting protection against CHMI using P. falciparum parasites heterologous to the vaccine strain has limited efficacy.

    Conclusion: RAS-vaccine and CPS-vaccine have the ability to give a potent vaccine efficacy against CHMI using P. falciparum parasites homologous to the vaccine strain when used in sufficiently high doses. Longterm protection against CHMI using P. falciparum parasites heterologous to the vaccine strain is limited and this in turn affects the use in endemic areas. In the future, the vaccine effect can be improved by higher doses, more infectious vaccine strains or vaccine cocktails. An alternative to RAS-vaccine and CPS-vaccine could be direct venous inoculation of late arresting GAP.

  • 100.
    Bladh, Emil
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Säkerhet vid val av apotek: Enkätundersökning om kunskap och uppfattningar om symboler för godkänt apotek2019Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    Aim: The aim of the degree project is to examine individual’s knowledge about symbols for approved pharmacy and how such a marking and other factors affect their choice of pharmacy from a safety perspective.

    Introduction: In a survey made by the Swedish Medical Products Agency (MPA) from 2008, 51 illegal websites targeting Swedish pharmacy customers were found. These websites illegally sold prescription pharmaceuticals without the requirement of a prescription from their customers. Shopping on illegal internet pharmacies can have great risks like contaminated drugs, lack of information about the drugs or that the drugs never gets delivered. To lower the risk that pharmacy customers accidently buys medications from the illegal online pharmacies, two symbols have been created for Swedish pharmacy customers, one by the MPA (figure 1) and one by the European Commission (figure 2). The idea is that the customer is supposed to click on one of the symbols on an online pharmacy’s website which is linked to a list for approved online pharmacies at the website of the MPA. If the customer finds the name and web address of the pharmacy on that list, the customer will know that the pharmacy is approved. But if the name and address isn’t found on the list, the pharmacy can be illegal, and the customer should avoid from shopping from the pharmacy.

    Material and methods: An electronic questionnaire with 10 question (Appendix A) was created in regard of the aim and sent out via the social platform “Facebook” through the students Facebook account. The survey included questions about which factors, from a security perspective, that influence the respondents to choose an online pharmacy and the respondents’ knowledge about the two symbols for controlling if an online pharmacy is approved. The results were analysed at a group level so that no individuals could be identified.

    Results and Discussion: The survey showed that a majority of the respondents had seen the Swedish symbol for approved pharmacy (figure 1) from the MPA (n=44, 59 %). However, a majority did not know what it means (n=57 or 77 %). Regarding the EU-symbol for approved pharmacy (figure 2), it turned out that most of the respondents had not seen it (n=58, 78 %) and even more didn’t know what it means (n=62, 84 %). The respondents in the study controlled pharmacies in different ways, for example making their own assessment if an online pharmacy seems safe (n=21, 51 %) or that they choose an online pharmacy that they have seen on some sort of commercial (n=17, 41 %) (Table II). For some it wasn’t something they thought about (n=10, 24 %) (Table II).

    Conclusions: The conclusion is that most of the respondents had seen the Swedish symbol for approved pharmacy but did not know what it means. Few respondents had seen the EU-symbol for approved pharmacy and even fewer knew what it means. The most common factors influencing the respondents’ choice of a pharmacy, from a security perspective, was by making their own assessment if the online pharmacy seems safe or choose a pharmacy which they have seen from a commercial. For some of the respondents, it wasn’t something they considered when choosing pharmacy.

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