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  • 201.
    Elmlund, Louise
    et al.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Söderberg, Pernilla
    Linnaeus University, Faculty of Health and Life Sciences, Department of Biology and Environmental Science.
    Suriyanarayanan, Subramanian
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Nicholls, Ian A.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences. Uppsala University.
    A Phage Display Screening Derived Peptide with Affinity for the Adeninyl Moiety2014In: Biosensors, ISSN 2079-6374, Vol. 4, no 2, p. 137-149Article in journal (Refereed)
    Abstract [en]

    Phage display screening of a surface-immobilized adenine derivative led to the identification of a heptameric peptide with selectivity for adenine as demonstrated through quartz crystal microbalance (QCM) studies. The peptide demonstrated a concentration dependent affinity for an adeninyl moiety decorated surface (KD of 968 ± 53.3 μM), which highlights the power of piezoelectric sensing in the study of weak interactions. 

  • 202.
    El-Sayed, Ashraf M.
    et al.
    New Zealand Inst Plant & Food Res Ltd, New Zealand.
    Unelius, C. Rikard
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences. New Zealand Inst Plant & Food Res Ltd, New Zealand.
    Suckling, David M.
    New Zealand Inst Plant & Food Res Ltd, New Zealand;Univ Auckland, New Zealand.
    Honey Norisoprenoids Attract Bumble Bee, Bombus terrestris, in New Zealand Mountain Beech Forests2018In: Journal of Agricultural and Food Chemistry, ISSN 0021-8561, E-ISSN 1520-5118, Vol. 66, no 50, p. 13065-13072Article in journal (Refereed)
    Abstract [en]

    Three varieties of honey of different dominant floral origin were found to attract social Hymenoptera, including the large earth bumble bee, Bombus terrestris, in a New Zealand mountain beech forest. This study was undertaken to identify volatile organic compounds that induce the attraction of bumble bees to honeybee (Apis mellifera) honey. We analyzed the chemical composition of the volatile organic compounds produced in three distinct varieties of honey (i.e., manuka, honeydew, and clover honey). The composition of the chemical profile of the three honey varieties differed in the quality and in the ratio of compounds in the headspace. o-Methoxyacetophenone was the main compound in the headspace of all three honey varieties. Among the 40 compounds identified in the headspace in the three varieties, only seven shared compounds (i.e., benzaldehyde, benzyl alcohol, phenylacetaldehyde, 2-phenylethanol, isophorone, 4-oxoisophorone, and o-methoxyacetophenone) were present in the headspace of the three honey varieties. The relative attractiveness of various blends of the seven common compounds found in the three honey varieties was tested for the attraction to bumble bees in a mountain beech forest. A binary blend of isophorone and 4-oxoisophorone at a ratio of 90:10 was the most attractive blend for both bumble bee workers and queens. A small number of honey bee workers were also attracted to the former binary blend. Our study represents the first identification of a honey-derived attractant for bumble bees and honey bees. The potential application of our finding for monitoring of bumble bees or to enhance crop pollination and help to tackle the current concern of a global pollination crisis is discussed.

  • 203.
    El-Sayed, Ashraf M.
    et al.
    New Zealand Institute of Plant & Food Research, New Zealand.
    Venkatesham, Uppala
    Unelius, C. Rikard
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences. New Zealand Institute of Plant & Food Research, New Zealand.
    Sporle, Andrew
    New Zealand Institute of Plant & Food Research, New Zealand.
    Perez, Jeanneth
    Macquarie Univ, Australia.
    Taylor, Phillip W.
    Macquarie Univ, Australia.
    Suckling, David M.
    New Zealand Institute of Plant & Food Research, New Zealand;Univ Auckland, New Zealand.
    Chemical Composition of the Rectal Gland and Volatiles Released by Female Queensland Fruit Fly, Bactrocera tryoni (Diptera:Tephritidae)2019In: Environmental Entomology, ISSN 0046-225X, E-ISSN 1938-2936, Vol. 48, no 4, p. 807-814Article in journal (Refereed)
    Abstract [en]

    The composition of the rectal gland secretion and volatiles emitted by female Queensland fruit fly, Bactrocera tryoni was investigated. Esters were found to be the main compounds in the gland extracts and headspace, while amides were the minor compounds in the gland extracts and headspace. Ethyl dodecanoate, ethyl tetradecanoate, ethyl (Z9)-hexadecenoate and ethyl palmitate were the main esters in the gland extracts, while ethyl dodecanoate and ethyl tetradecanoate were the main esters in the headspace. Four amides (N-(3-methylbutyl)acetamide), N-(2-methylbutyl)propanamide, N-(3-methylbutyl)propanamide, and N-(3-methylbutyl)-2-methylpropanamide were found in the gland extracts and the headspace. Among the amides, N-(3-methylbutyl)acetamide and N-(3-methylbutyl)propanamide were the main amides in the gland extracts and the headspace.Traces of three spiroacetals were found both in the gland extracts and in the headspace. (E,E)-2,8-Dimethyl-1,7-dioxaspiro[5.5]undecane, (E,E)-2-ethyl-8-methyl-1,7-dioxaspiro[5.5]undecane, (E,E)-2-propyl-8-methyl-1,7-dioxaspiro[5.5]undecane. All compounds found in the headspace were present in the extract of the rectal gland suggesting that the rectal gland is the main source of the headspace volatiles, whose function remains to be elucidated.This is the first comprehensive chemical analysis of the rectal gland secretions and volatiles of female B. tryoni, and further laboratory and field bioassays are required to determine the function of compounds identified in this study. Discovery of the same amides previously identified in the male rectal gland in the female rectal gland raises questions about the pheromonal role previously suggested for these compounds.

  • 204.
    Elvingson, Ebba
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Art- och genusbestämning av bakterier direkt från blododlingar med MALDI-TOF MS2014Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [sv]

    Sepsis är ett allvarligt tillstånd som uppstår när bakterier går från vävnad till blodbanan. Positiva blododlingar odlas på agarplattor och bakterier analyseras med Matrix Assisted Laser Desorption Ionisation Time-of-flight Mass spectrometry (MALDI-TOF MS) där prov blandas med en matrix och sedan bestrålas med laser. Proteinerna i provet joniseras och rör sig mot en detektor, vilket ger ett m/z-spektrum som jämförs med referensspektrum i en databas och ett score-värde erhålls över hur väl analyten liknar referensen. Arbetets syfte var att undersöka möjligheten att direktidentifiera bakterier från blod med en viss preparation innan analys med MALDI-TOF MS och på så vis möjliggöra snabbare preliminära svar samt undersöka möjligheten att särskilja Staphylocoocus aureus och koagulasnegativa stafylokocker. Innan analys med MALDI-TOF MS centrifugerades blod från positiva blododlingar blod i flera steg med 5 % natriumkloridlösning (NaCl-metoden). Dessutom testades ett kommersiellt kit (Sepsityper, Bruker Daltonics). Med NaCl-metoden sågs korrekt identifiering hos 66 % av inokulerade proverna. Av blododlingar innehållande med S. aureus respektive koagulasnegativa stafylokocker identifierades 60 % respektive 43 % av bakterierna korrekt. Med Sepsiptyper erhöll 58 % av proverna godkänt score-värde. Slutsatsen blev att det är möjligt att identifiera bakterier direkt från blod efter viss preparation, men metoden bör utvecklas mer då det fanns en signifikant skillnad i score mellan NaCl-metoden och nuvarande metod. Det är dock möjligt att skilja mellan Staphylococcus aureus och koagulasnegativa stafylokocker. Fler studier är nödvändiga för att avgöra möjligheten att föra in någon av metoderna i rutindiagnostiken.

  • 205.
    Emrin, Karin
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Effekten av farmaceutiska läkemedelsgenomgångar hos multimedicinerade äldre patienter2017Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    The population of elderly people in Sweden is increasing and old patient have higher risk of suffering from diseases that require treatment. Physiological changes and multi-medication increase the risk of drug-related problems. The medication reviews can detect, correct and prevent drug-related problems which will improve the safety and quality in the drug treatment. Medication reviews are mainly conducted by physicians in health care. However, with the expertise of pharmacists as a part of the health care team, benefits such as lower drug costs and better quality of life can be seen.

    The aim of this study was to investigate the effects of pharmacist-led medication review at multi-medicated elderly patient.

    This study was a literature study and the articles were collected from PubMed. A total of five studies were reviewed.

    The pharmacutical medication review of the multi-medicated elderly people were conducted at community pharmacies in Netherlands and Schwitzerland in three of the studies and two of them were conducted within the Swedish primary health care. The results from the pharmacutical medical reviews revealed 1,2 to 4,1 drug-related problems/patient. The most common problems were ’over-treatment, ’non-compliance’, ’expired indication’, ’unnecessary therapy’ and ’adverse drug effect’. The most common intervention the pharmacist suggested, in all of the studies, was to stop the treatment. Implemented interventions were reported in varying implementation rate in four of the studies, from 3,9% to 56%. Two of the studies reported a reduction of drug-related problems/patient. From 4,1 to 3,3 drug-related problems/patient and from 1,7 to 1,3 drug-related problems/patient.

    The analyzes of the studies show that pharmacist-led medication reviews at community pharmacies and in the primary health care can reduce the number of drug-related problems. Not all of the studies presented results of drug-related problem/patient after the pharmacist´s proposed intervention. However, the results of implemented interventions indicate that pharmaceutical medication reviews have a positive effect for multi-medicated patients. In order to decrease the number of drug-related problems in elderly patients, more knowledge with regard to pharmaceutical treatment of elderly as well as better cooperation between helthcare and pharmacies is required. 

  • 206.
    Emstrand, Anna
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Kan förändring av kost förbättra sjukdomen reumatoid artrit (RA)?: Vegandiet med eller utan gluten och medelhavsdiet2019Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [sv]

    Reumatoid artrit (RA) är en kronisk inflammatorisk ledsjukdom som karakteriseras av ledassocierad smärta, svullnad och funktionsförlust på grund av stelhet i lederna. RA är en av de vanligaste inflammatoriska sjukdomarna och drabbar cirka 0,5 % av Sveriges befolkning. Insjuknandefrekvensen är som högst hos kvinnor i åldern mellan 50 till 65 år och den främsta enskilda riskfaktorn till sjukdomen är rökning. Sjukdomen är inte enskilt livshotande, men den medför risker som osteoporos och kardiovaskulära sjukdomar vilket kan minska livslängden. Orsaken till sjukdomen är ännu inte känd, men immunstörning med en autoimmunitet har kunnat påvisa antikroppar som reagerar mot kroppsegna peptider. Behandlingen kan se olika ut beroende på sjukdomsaktivitet. Behandlingsalternativen som finns är steroider, NSAID (non-steroid anti-inflammatory drug) DMARD (disease-modifying antirheumatic drug) och biologiska läkemedel. Dessa läkemedel har sällan total effekt och därför prövar ofta RA-patienter alternativa interventioner som kosttillskott. Syftet med examensarbetet var att studera om kostintervention kan påverka grundbehandlad RA-sjukdom och i så fall hur. En litteraturstudie genomfördes via litteratursökningar på databasen PubMed. Sju studier valdes ut, efter matchning av kriterier och utvärderades därefter. Resultatet visade att vegandiet med eller utan gluten och medelhavsdiet gav en förbättrad effekt i definitionen att allmänhälsan blev bättre och att RA-symptom minskade. Vilka effekter det gav och hur pass mycket varierade. Kosten är nödvändig för kroppens funktioner och eftersom vegandiet och medelhavsdiet är växtbaserade så är de även gynnsamma för miljön. Framtida studier av kostintervention på grundbehandlade RA-patienter skulle ge ökad evidens med fler deltagare, längre studieduration och en ökad observation av andra livsstilsfaktorer.

  • 207.
    Enbom, Nathalie
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Behandlingsalternativ vid egentlig depression: en jämförelse mellan agomelatin och SSRI/SNRI2018Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    Aim: The aims of the study were to compare the effects on depressive symptoms and insomnia between agomelatine and SSRIs/SNRIs in adult patients with major depression disorder.

    Method: Materials were collected from the database Pubmed and selected through the aims of the study and certain selection criterias. It was required that the studies fulfilled at least one of the study´s aims to be eligible for inclusion. Eight randomised clinical trials were included in the study. The results from the studies were compared according to statistical and clinical significance.

    Results: Depressive symtoms were reduced both with agomelatin and SSRIs/SNRIs. Generally the rates of respone and remission were similar of agomelatine and SSRIs/SNRIs. There were advantages for agomelatine in the individual studies concerning rates of respone and remission. Six of the included studies investigated the effect on insomnia. In a majority of these studies agomelatine caused a statistically significant improvement compared to SSRIs/SNRIs. Clinically, both agomelatine och SSRIs/SNRIs improved most of the variables related to insomnia that were examinated according to patient-reported outcome results.

    Conclusion: Statistically both SSRIs/SNRIs and agomelatine achieved similiar effects on depressive symptoms. In the majority of the included studies that examinated effect on insomnia agomelatine showed a statistically significant improvement compared to SSRIs/SNRIs. Clinically, agomelatine is viewed as a viable option for adult patients with major depressive disorder with unsuccessful response or remission from SSRIs/SNRIs. A similiar clinical relevance were shown for agomelatine and SSRIs/SNRIs concerning improvement of insomnia according to patient-reported outcome results.

  • 208.
    Engberg, Anna E.
    et al.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences. Region Skåne.
    Nilsson, Per H.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences. Oslo Univ Hosp, Rikshosp, Norway;Univ Oslo, Norway.
    Huang, Shan
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Fromell, Karin
    Uppsala University.
    Hamad, Osama A.
    Uppsala University.
    Mollnes, Tom Eirik
    Univ Oslo, Norway;Univ Tromsö, Norway.
    Rosengren-Holmberg, Jenny P.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences. Swedish Natl Lab Forens Sci, Linköping.
    Sandholm, Kerstin
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Teramura, Yuji
    Uppsala University;Univ Tokyo, Japan.
    Nicholls, Ian A.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences. Uppsala University.
    Nilsson, Bo
    Uppsala University.
    Nilsson Ekdahl, Kristina
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences. Uppsala University.
    Prediction of inflammatory responses induced by biomaterials in contact with human blood using protein fingerprint from plasma2015In: Biomaterials, ISSN 0142-9612, E-ISSN 1878-5905, Vol. 36, p. 55-65Article in journal (Refereed)
    Abstract [en]

    Inappropriate complement activation is often responsible for incompatibility reactions that occur when biomaterials are used. Complement activation is therefore a criterion included in legislation regarding biomaterials testing. However, no consensus is yet available regarding appropriate complement-activation-related test parameters. We examined protein adsorption in plasma and complement activation/cytokine release in whole blood incubated with well-characterized polymers. Strong correlations were found between the ratio of C4 to its inhibitor C4BP and generation of 10 (mainly pro-inflammatory) cytokines, including IL-17, IFN-gamma, and IL-6. The levels of complement activation products correlated weakly (C3a) or not at all (C5a, sC5b-9), confirming their poor predictive values. We have demonstrated a direct correlation between downstream biological effects and the proteins initially adhering to an artificial surface after contact with blood. Consequently, we propose the C4/C4BP ratio as a robust, predictor of biocompatibility with superior specificity and sensitivity over the current gold standard. (C) 2014 Elsevier Ltd. All rights reserved.

  • 209.
    Engberg, Anna E.
    et al.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Nilsson, Per H.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences. Univ Oslo, Rikshosp, Univ Hosp, Norway.
    Sandholm, Kerstin
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Huang, Shan
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Mollnes, T. E.
    Nicholls, Ian A.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences. Uppsala University.
    Nilsson, Bo
    Uppsala university.
    Nilsson Ekdahl, Kristina
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences. Uppsala university.
    The ratio between C4 and C4BP adsorbed to artificial materials is a new predictor for biocompatibility2013In: Molecular Immunology, ISSN 0161-5890, E-ISSN 1872-9142, Vol. 56, no 3, p. 309-309Article in journal (Other academic)
  • 210.
    Engdahl, Inger
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Postoperative confusion is related to low levels of cobalamine and folate in elderly patients operated for a hip fracture2017Independent thesis Advanced level (degree of Master (One Year)), 20 credits / 30 HE creditsStudent thesis
  • 211.
    Engreni, Soumaya
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Folate, fibre and ash in pulses from Öland2017Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
  • 212.
    Eriksson, Annabelle
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Vad har Spironolakton för effekt på hjärta, kärl och det sympatiska nervsystemet hos hjärtsviktspatienter?2014Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [sv]

    Hjärtsvikt är en folksjukdom där prevalensen har uppskattats till cirka 2 %. Sjukdomen innebär att hjärtats funktion är försämrad. Idag behandlas hjärtsvikt vanligtvis med ACE-hämmare, betablockerare och ibland spironolakton. Spironolakton är en mineralkortikoidreceptorantagonist, som i RALES-studien (1999) har visat goda effekter på mortalitets- och morbiditetsreduktion hos hjärtsviktspatienter när den gavs som tillägg till ACE-hämmare. Idag är det ännu inte helt känt hur läkemedlet utövar sin effekt. Syftet med detta arbete är att undersöka vad spironolakton har för effekt på hjärta, blodkärl samt det sympatiska nervsystemet hos hjärtsviktspatienter. En litteraturstudie gjordes där sju studier utvärderades. Två av de utvalda studierna behandlade spironolaktons effekt på blodkärlen, två på hjärtremodelleringen, två på hjärtfibrosen och en på det sympatiska nervsystemet. Resultaten från studierna visade att spironolakton har goda effekter på kärlen bland annat genom att öka biotillgängligheten av kväveoxid. Läkemedlet har också goda effekter på hjärtremodelleringen, troligtvis framförallt genom att minska fibrosbildningen. Dessutom har spironolakton fördelaktiga effekter på det sympatiska nervsystemet. Många av spironolaktons effekter beror troligtvis på dess förmåga att blockera aldosterons effekt. De fysiologiska effekter som visades i detta arbete kan sannolikt ge mortalitets- och morbiditetsreduktion hos verklighetens hjärtsviktspatienter då läkemedlet adderas till modern basbehandling. I RALES var betablockeraranvändning ovanlig och klinikens patienter motsvarade inte verklighetens patienter. Därför kan en modern studie liknande RALES, men på verklighetens hjärtsviktspatienter, ge svar på frågan om spironolakton idag är ett effektivt läkemedel för behandling av hjärtsvikt.

  • 213.
    Eriksson, Caroline
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Vilken är allmänhetens attityd till receptfria smärtstillande läkemedel?: En enkätundersökning2013Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [sv]

    Syftet med detta arbete var att undersöka allmänhetens attityd till användning av receptfria smärtstillande läkemedel. Som metod användes en nätbaserad enkätundersökning. Länken till enkäten marknadsfördes via Facebook och via utskick till de närmaste vännerna. Av de 126 yngre, huvudsakligen kvinnor, med en utbildningsnivå över genomsnittet i landet, och som rekryterades till att besvara den nätbaserade enkäten framkom att fyra av fem använde sporadiskt värktabletter. Fyra av tio använde endast ett läkemedel och var tredje använde två olika läkemedel. Åtta av tio använde paracetamol och en av fyra ibuprofen. En av fem använde enbart NSAID-preparat. En tredjedel använde även receptbelagda värktabletter. Värktabletterna användes i drygt hälften av fallen mot huvudvärk. Hälften av respondenterna skaffade sig information via bipacksedlar eller hälso- och sjukvårdspersonal. 15 % angav att de inte skaffade sig någon information om receptfria värktabletter. Drygt åtta av tio köper sina värktabletter på apotek och nästan alla tycker att det är bra med en 18-årgräns för inköp av värktabletter utanför apoteken. En tredjedel anser att värktabletter är ofarliga om man använder dem enligt doseringsanvisningarna. En tredjedel ser risker med användningen även om man följer doseringsanvisningarna. En av fyra ser stora risker med dem. Det fanns en trend mot att de med högst utbildning och de i åldersintervallet 31-65 år såg fler risker med användningen av värktabletter än övriga.

  • 214.
    Eriksson, Oskar
    et al.
    Uppsala University, Sweden.
    Mohlin, Camilla
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Nilsson, Bo
    Uppsala University, Sweden.
    Nilsson Ekdahl, Kristina
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences. Uppsala University, Sweden.
    The Human Platelet as an Innate Immune Cell: Interactions Between Activated Platelets and the Complement System2019In: Frontiers in Immunology, ISSN 1664-3224, E-ISSN 1664-3224, Vol. 10, p. 1-16, article id 1590Article, review/survey (Refereed)
    Abstract [en]

    Platelets play an essential role in maintaining homeostasis in the circulatory system after an injury by forming a platelet thrombus, but they also occupy a central node in the intravascular innate immune system. This concept is supported by their extensive interactions with immune cells and the cascade systems of the blood. In this review we discuss the close relationship between platelets and the complement system and the role of these interactions during thromboinflammation. Platelets are protected from complement-mediated damage by soluble and membrane-expressed complement regulators, but they bind several complement components on their surfaces and trigger complement activation in the fluid phase. Furthermore, localized complement activation may enhance the procoagulant responses of platelets through the generation of procoagulant microparticles by insertion of sublytic amounts of C5b9 into the platelet membrane. We also highlight the role of post-translational protein modifications in regulating the complement system and the critical role of platelets in driving these reactions. In particular, modification of disulfide bonds by thiol isomerases and protein phosphorylation by extracellular kinases have emerged as important mechanisms to fine-tune complement activity in the platelet microenvironment. Lastly, we describe disorders with perturbed complement activation where part of the clinical presentation includes uncontrolled platelet activation that results in thrombocytopenia, and illustrate how complement-targeting drugs are alleviating the prothrombotic phenotype in these patients. Based on these clinical observations, we discuss the role of limited complement activation in enhancing platelet activation and consider how these drugs may provide opportunities for further dissecting the complex interactions between complement and platelets.

  • 215.
    Eriksson, Theres
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Effekten av statiner för förebyggande av hjärt- och kärlsjukdomar2017Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [sv]

    Statiner är ett av de mest förskrivna läkemedlen i Sverige. Det används för att sänka kolesterolvärdet i blodet för att förebygga hjärt- och kärlsjukdomar. Höga kolesterolvärden anses vara en viktig riskfaktor för hjärtsjukdom. Det är främst höga halter av lipoproteinet LDL som anses vara en riskfaktor för hjärtsjukdomar eftersom denna bidrar till aterosklerosprocessen. Statiner används både som primärprevention (förebyggande) och som sekundärprevention (efter personen drabbats av hjärtsjukdom). Syftet med arbetet var att med hjälp av metaanalyser och kliniska studier undersöka effekten av statiner för prevention av hjärt- och kärlsjukdomar. Studierna som inkluderades i arbetet hittades genom sökning på Pubmed. Fem studier inkluderades i arbetet. Dessa visade att statiner minskar dödligheten och insjuknande i hjärt- och kärlhändelser vid sekundär prevention, att de kan minska risken att insjukna vid primär prevention men att statiner inte påverkar dödligheten vid primär prevention. En av studierna visade att statiner ger en ökad risk att drabbas av myopati, leversjukdom och diabetes typ 2. Resultatet av detta arbete visar att statiner har effekt för sekundär prevention och att personer som haft hjärtsjukdom kan behandlas med statiner. Statiner visade sig dock inte effektiva vid primär prevention, vilket kan tyda på att statiner skrivs ut i för hög utsträckning idag och att statiner inte bör ges till personer som inte är sjuka i hjärtsjukdom i första hand.

  • 216.
    Erixon, Annie
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Ridterapi som habiliteringsverktyg: Förbättrar ridterapi koordination hos barn med cerebral pares?2018Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    Cerebral palsy is a brain injury that gives the patient muscle contraction and spasticity. This causes movement disorders to a different extent. Cerebral palsy is a, usually congenital, chronic condition which can be habilitated with the help of proper care. Hippotherapy uses the horse’s movements to treat the patient. The horse’s varied, rhythmic, repetitive movements provide a physical and sensory feedback to the rider that is believed to improve the body's postural control, strength and balance of the patient. The aim of this literaturestudy was to find out if hippotherapy can improve coordination in children with Cerebral palsy. Nine articles has been used in this study. The articles were found in Pubmed database. The results shows that hippotherapy can improve mobility, functional performance, fine motor capacity, balance and postural control in children with Cerebral palsy. The improvements last over time, at least for children with GMFCS I-III. The studies that has been used are all small and diverse. Bigger and more specified studies are needed to gain safer results.           

  • 217.
    Eskilsson, Moa
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Kombinerade p-pillers påverkan på muskulär styrka och kondition: en systematisk litteraturstudie med metaanalys2018Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    The effects of contraceptives on athletic performance are not easy to survey. That makes it difficult for women to make an informed decision regarding their contraceptive use. Existing research suggest that oestrogen and progesterone have an effect on muscle strength and fitness. The objective of this thesis was to examine the effect of endocrine contraception on athletic performance. The study was designed as a systematic review with meta-analysis. The PubMed data base was used to search for relevant articles. Meta-analysis was performed on hand strength, knee extension strength, peak oxygen uptake, minute ventilation and peak heart rate. The meta-analysis showed no significant effect for any of the performance variables. The conclusion is that if endocrine contraceptives have an effect on athletic performance the effect is small. Methodological issues may have affected the results. The included studies are of low quality and generally expresses selection bias. More extensive randomized controlled studies are needed to confirm the results.

  • 218.
    Evertsson, Kim
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Protein expression and modifications in denervated atrophic and hypertrophic skeletal muscle2014Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Skeletal muscle comprises about 45% of the total body weight. It is the largest tissue in the body, vital for maintaining posture, produce locomotion, breathing but also functions as a large reservoir of proteins. Regulation and maintenance of muscle mass is a delicate process and is determined by the balance between protein synthesis and degradation. Following denervation skeletal muscles change their functional and structural properties. Most muscles start to lose weight due to the inactivity caused by denervation and become atrophic, whereas the hemidiaphragm initially increases in weight the first 6-10 days and becomes hypertrophic, followed by a decrease in weight. The aim of this thesis was to examine the expression and phosphorylation of factors potentially involved in the regulation of skeletal muscle mass in denervated atrophic hind-limb muscles and in denervated hypertrophic hemidiaphragm muscles in mice. Another aim was to identify markers that could be linked to lysosomal and autophagic activities in denervated muscle.Factors of the Akt/mTOR pathway were studied and results indicative of increased protein synthesis were obtained in both denervated atrophic and hypertrophic muscles. This suggests that skeletal muscle atrophy following denervation is more likely to depend on increased protein degradation rather than an overall decrease in protein synthesis (paper I). A differential response of MK2 Thr317 phosphorylation in denervated atrophic and hypertrophic muscles was confirmed, without corresponding changes in phosphorylation of p38, indicating that other factors than p38 are responsible for this differential response, possibly Hsp70. Factors other than MK2 may be responsible for the phosphorylation of Hsp25, since increased levels of phosphorylated Hsp25 were seen in all denervated muscles studied (paper II). Results also suggested FoxO1 and MuRF1 to have potential roles in tissue remodeling that occurs after denervation (paper III). Immunoreactivity for the lysosomal marker Lamp1 and for the autophagic marker protein Lc3 was observed in characteristic ring-like structures in transverse sections of denervated muscle fibers (paper IV).  

  • 219.
    Evertsson, Kim
    et al.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Fjällström, Ann-Kristin
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Norrby, Marlene
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Tågerud, Sven
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    p38 mitogen-activated protein kinase and mitogen-activated protein kinase-activated protein kinase 2 (MK2) signaling in atrophic and hypertrophic denervated mouse skeletal muscle2014In: Journal of Molecular Signaling, ISSN 1750-2187, E-ISSN 1750-2187, Vol. 9, no 2Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: p38 mitogen-activated protein kinase has been implicated in both skeletal muscle atrophy and hypertrophy. T317 phosphorylation of the p38 substrate mitogen-activated protein kinase-activated protein kinase 2 (MK2) correlates with muscle weight in atrophic and hypertrophic denervated muscle and may influence the nuclear and cytoplasmic distribution of p38 and/or MK2. The present study investigates expression and phosphorylation of p38, MK2 and related proteins in cytosolic and nuclear fractions from atrophic and hypertrophic 6-days denervated skeletal muscles compared to innervated controls.

    METHODS: Expression and phosphorylation of p38, MK2, Hsp25 (heat shock protein25rodent/27human, Hsp25/27) and Hsp70 protein expression were studied semi-quantitatively using Western blots with separated nuclear and cytosolic fractions from innervated and denervated hypertrophic hemidiaphragm and atrophic anterior tibial muscles. Unfractionated innervated and denervated atrophic pooled gastrocnemius and soleus muscles were also studied.

    RESULTS: No support was obtained for a differential nuclear/cytosolic localization of p38 or MK2 in denervated hypertrophic and atrophic muscle. The differential effect of denervation on T317 phosphorylation of MK2 in denervated hypertrophic and atrophic muscle was not reflected in p38 phosphorylation nor in the phosphorylation of the MK2 substrate Hsp25. Hsp25 phosphorylation increased 3-30-fold in all denervated muscles studied. The expression of Hsp70 increased 3-5-fold only in denervated hypertrophic muscles.

    CONCLUSIONS: The study confirms a differential response of MK2 T317 phosphorylation in denervated hypertrophic and atrophic muscles and suggests that Hsp70 may be important for this. Increased Hsp25 phosphorylation in all denervated muscles studied indicates a role for factors other than MK2 in the regulation of this phosphorylation.

  • 220.
    Fahlgren, Viktoria
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Utveckling av en C-vitaminberikad tofuprodukt: Studie av C-vitaminhalt under process och förvaring2017Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    Tofu is a plant based product made from soybeans, water and a coagulant. The coagulant together with heating enables the formation of a soy curd (tofu). The proteins that dominates in soybeans are β-conglycinin (7S) and glycinin (11S). The composition of the proteins differs between soybean cultivars, which also affects the formation of the tofu. The object in this study was to evaluate the vitamin C content and the stability of vitamin C during processing and storage in an ecological tofu-product after enrichment of Sea Buckthorn to increase the vitamin content. Furthermore, the use of germinated soy beans instead of soaked soybeans in the production of tofu was evaluated. When Sea Buckthorn was added to the soymilk it resulted in a decrease in pH from 6.3 to 5.5, which affected the formation of the soy curd negatively as the optimal pH is between 6.0 and 6.5. By adding alkali to reach pH 6.3 it was possible to achieve a soy curd when Sea Buckthorn powder was added. Sea Buckthorn increased the vitamin C content in the product to 32 mg/250 g but only 10% (about 3 mg) remained after four weeks storage. The loss of vitamin C was large in both processing and storage of the tofu. An additional loss of 7- 14% was detected during 10 minutes heating (60°C). Germination of soybeans did neither affect the amount of protein, nor the vitamin C content in tofu. To produce a tofu with more than 15% of RDI for vitamin C in one serving (100 g) the amount berry powder to be added in the production of 250 g tofu must not be less than 31 g (400 mg vitamin C), based on losses up to 90-95% during the process and storage. Hence the huge amount of berry powder that must be added, other ways to decrease the degradation of vitamin C is necessary to be investigated.

  • 221.
    Farhang, Hoda
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Hur effektiv och säker är sativex jämfört med gabapentin som tillägg till opioider vid cancerrelaterad neuropatisk smärta?2018Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    Background: Pain is one of the most prominent and disturbing symptoms reported by cancer patients. Appropriate pain relief is obtainable in more than 75 % of the patients with optimized analgesic treatment. Opioids and non-opioids are being utilized in cancer pain treatment and analgesics are used to improve the effectiveness of opioids. Gabapentin is primarily used as an anti-epileptic drug that is also recommended as the first-choice drug in treatment of neuropathic pain. Research is being conducted to evaluate cannabinoids as adjuvans analgesics. Sativex is the extract of cannabis sativa plant and is used to treat and ease moderate to severe symptoms of spasticity caused by multiple sclerosis (MS) in Sweden. Several scientific studies have recently studied sativex with positive results and the drug is currently being used in some countries in treatment of resistant cancer-related neuropathic pain.

    Purpose: The purpose of this paper was to conduct a scientific study and examine whether sativex is as efficient and secure as gabapentin and thus an option as addendum in cancer-related neuropathic pain when the treatment with only opioids is not sufficient for pain relief.

    Method: This literature study is based on examination of six clinical scientific studies. The articles are searched in PubMed database, the articles are about examination of effectiveness and security of gabapentin and sativex compared to placebo or other equivalent drugs in cancer patients suffering from neuropathic pain.

    Results: Two of the studies that compared gabapentin with placebo and one that compared Gabapentin with Amitriptylin (an anti depressive drug) showed that gabapentin was an efficient adjuvans analgesic that led to statistically significant pain relief in patients suffering from cancer. The side effects were mild to moderate in all three studies, and overdose of the study-drug was tolerated well. One of three studies evaluating efficacy and safety of sativex showed that the change in daily average pain score during two weeks of treatment was statistically significant in patients in the sativex-group compared to the group of patients receiving THC-extract and placebo-group. In the second study, sativex was compared within three different dosage groups (low, middle and high) as well as placebo and the result showed that sativex had significant pain relief only in patients receiving low dose of sativex. The third study showed that sativex led to pain relief in patients receiving sativex compared to those receiving placebo however the effect was not statistically significant. Dizziness, nausea and vomiting were the most common side effects in all three studies. The side-effects were mild to moderate and no serious safety issues were observed in the first and third studies. In the second study on the other hand, the patients were encouraged to maintain a stable opioid-dose which resulted in more side-effects.

    Conclusion: All three studies that examined the effectivness of sativex showed improvement on sleeping quality as well as pain relief, where two of the studies showed statistically significant pain relief in patients suffering from neuropathic cancer-pain. Studies on cannabinoids are quite controversial and there are not many global studies available that have studied its safety and efficacy in the treatment of neuropathic cancer-related pain. It is however a growing and upcoming area that is also expected to grow multiply in turnover which should enable more studies being conducted. These results show that sativex has the potential of being a good alternative in the treatment of neuropathic cancer-related pain. Sativex is also effective in low doses without the need for increases over time, furthermore side effects are mild to moderate and possible overdose is well managed by patients.

    Gabapentin been used in pain management in neuropathic cancer-pain for a long time with minimal side effects. Sativex, on the other hand, is quite new and there are not many studies performed on the medicine. Furthermore, there are no studies comparing sativex and gabapentin which makes it very difficult to conclude whether it holds the same safety and may act as a good alternative to gabapentin. In future studies, sativex should be compared to medicines used today such as gabapentin in order to prove its ability of being an alternative.

  • 222.
    Faxe Borgryd, Emma
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Har energidryck någon kognitiv effekt i kombination med alkohol?: Med fokus på komponeneten koffein2014Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    Background: Energy drinks have been found in everyday-stores since 1997 and their popularity have increased over time. Consumtion of energy drinks takes place because of their ability to increase concentration and to decrease fatigue but also because of the popularity the drinks have got. Target groups for these stimulating beverages are adolescents and young adults. Energy drinks contain caffeine, taurine, glucuronolacton, carbohydrates and B-vitamins and voices have been raised about the eligibility for young people to ingest large quantities of these kinds of substances. Because of the properties of these substances it has become popular to mix energy drinks and alcoholic beverages to make up for the negative effects of alcohol and to be able to drink larger quantaties.

    Aim: The aim of this literature work was to investigate cognitive effects of the combination of caffeine in terms of energy drinks and alcohol and to determine if these effects could be harmful.

    Method: This literature work is based on five scientific articles retrieved from PubMed. Inclusion criteria for selection of the articles were examination of the effects of a combined use of alkohol and energy drinks.

    Results: A combination of energy drinks and alcohol can give a larger intake of alcohol and/or an overestimate of a persons abilities (for example to drive). Some effects can be seen in the perception of alcohol effects by simultaneous intake of alcohol and energy drinks because of the effect of caffeine.

    Discussion: There are many factors that can have an influence when it comes to effects of a combination of energy drinks and alcohol. Caffeine (in energy drinks) can have some impact on the perception of alcohol effects but also use of tobacco, contraceptives and energy states in the body can make a difference. Expectations that some substances could have an influence (placebo effect) might as well give an effect.

  • 223.
    Femzén, Malin
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Är biosimilarer till adalimumab lika effektiva och säkra vid behandling av reumatoid artrit som det biologiska referensläkemedlet adalimumab (Humira)?2018Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    Rheumatoid arthritis (RA) is a type of rheumatic disease where pronounced inflammation occurs in several joints along with pain and stiffness. The inflammation occurs as a result of an autoimmune reaction. In Sweden, approximately 1% of the population has RA and the disease is 2-3 times more common among women than men. One of the proinflammatory cytokines that plays a major role in RA is tumor necrosis factor (TNF). TNF is produced primarily by macrophages in the synovial membrane and has been shown to regulate release of other cytokines like IL-1 and IL-6. TNF also contributes to the release of metalloproteases from fibroblasts, reduced synthesis of proteoglycan from chondrocytes and to monocytes differentiate into osteoclasts. In this way, TNF contributes to joint destruction. Adalimumab (Humiraâ) is a TNF-inhibitor used in the treatment of RA. Humira is a humanized monoclonal antibody that binds to TNF and neutralizes the effects that TNF exerts and thus reduces symptoms and inhibits the progression of RA. In 2018, Humira is expected to be exposed to biosimilars competition. Biosimilars contains a version of the active substance in the biological reference drug and in order for a biosimilar to be approved it is necessary that they have comparable effect and safety as the reference drug. The purpose of this literature study was to investigate whether biosimilars to adalimumab are as effective and safe in the treatment of RA as the biological reference drug Humira. The five articles analyzed in this literature study were found through a search in the PubMed database with the words "rheumatoid arthritis", "adalimumab" and "biosimilar". In total, this resulted in 38 hits, of which 5 were selected. According to the results seen in this literature study, it can be noted that the five biosimilars investigated had similar effect as the reference drug adalimumab (Humira) in the treatment of RA. Four out of five studies also showed that the immunogenicity between the biosimilar and Humira was similar. Similar side effects occurred in both treatment groups and treatment with a biosimilar did not give more or more serious side effects than treatment with Humira. The launch of biosimilar adalimumab is likely to result in lower treatment costs and cost savings, as a result of the price competition that may occur between biosimilar adalimumab and the reference drug Humira. How much the cost will fall is hard to predict, but if there is a 58% reduction previously seen with other launched biosimilars, it can result in a cost saving of SEK 635 million. However, the amount of price reduction remains to be seen.

  • 224.
    Ferawati, Ferawati
    et al.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences. Linneaus University.
    Hefni, Mohammed E.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences. Mansoura University, Egypt.
    Witthöft, Cornelia M.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Flours from Swedish pulses: Effects of treatment on functional properties and nutrient content2019In: Food Science & Nutrition, E-ISSN 2048-7177, p. 1-11Article in journal (Refereed)
    Abstract [en]

    Despite the high nutritional profile in pulses, pulse consumption in Sweden is still low. However, the recent increase in consumption of sustainable and locally produced food in Sweden is driving demand for a versatile, functional pulse-based ingredient that can be incorporated into different food products. This study assessed different treatments (boiling, roasting, and germination) when preparing flour from domes- tically grown pulses (yellow pea, gray pea, faba bean, and white bean). Functional properties (water and oil absorption capacity, emulsion and foaming properties, and gelation concentration) of the flours produced following different treatments and their nutrient content (total dietary fiber, total choline, and folate content) were de- termined. Depending on pulse type, all treatments increased (p < .001) water ab- sorption capacity up to threefold and gelation concentration up to twofold, whereas emulsion activity and foaming capacity decreased by 3%–33% and 5%–19%, respec- tively, compared with flour made from raw pulses. All treatments also had a signifi- cant effect (p < .001) on nutrient content. Total dietary fiber increased (p < .02) by 11%–33%, depending on treatment and pulse type. Boiling decreased (p < .001) total choline and folate content in all pulse flours, by 17%–27% and 15%–32%, respec- tively. Germination doubled folate content (p < .001) in flour from both pea types compared with flour from the raw peas. In conclusion, treated pulse flours could be useful in food applications such as coating batter, dressings, beverages, or bakery goods, to improve the content of fiber, total choline, and folate.

  • 225.
    Fernando, Cathrine
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Mipomersen, an apolipoprotein B synthesis inhibitor: A literature study analyzing efficacy and safety when used for treating patients with familial hypercholesterolemia2019Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    Familial hypercholesterolemia is a genetic disease affecting about 10 million people around the world. Those who carry the disease have a very high risk of developing cardiovascular diseases and commonly encounter myocardial infarction at the early age of 40. Therefore, a diagnosis and immediate treatment are very important for these patients. Despite many combinations of available drugs, there are many patients who still cannot reach the desired cholesterol levels.

    Mipomersen is a new lipid-lowering drug which inhibits the synthesis of apolipoprotein B, a common component of lipoproteins such as low-density lipoprotein. Inhibition of this protein leads to reduced production of these lipoproteins and reduces the risk of cardiovascular diseases. The drug is currently only indicated for treating patients with homozygous familial hypercholesterolemia.  Unfortunately, there have been many reports of adverse events in patients using mipomersen which has proven problematic.        

    The aim of this thesis is to analyze the efficacy and safety of mipomersen when treating patients with familial hypercholesterolemia. This has been done by searching for five clinical trials in the database Web of Science. The studies were required to include patients with familial hypercholesterolemia, use mipomersen as the study drug and analyze its effect and safety.  

    The studies showed that mipomersen has a very good effect in decreasing low-density lipoproteins as well as other lipoproteins in comparison to placebo. Many of the patients who were treated with mipomersen displayed several adverse events and the most common were injection-site reaction and influenza-like symptoms. Elevated levels of aminotransaminase and increased fat deposit in the liver were also common.

    Based on the five clinical trials analyzed in this thesis, mipomersen is an effective lipid-lowering drug which reduces low density lipoprotein cholesterol, apolipoprotein B and lipoprotein (a) in patients with familial hypercholesterolemia. Elevations in alanine aminotransferase and aspartate aminotransferase are common in patients treated with mipomersen. This could indicate a negative impact on the liver. To be more certain of its safety profile, more research could be needed. There are however, new treatments that combines statins and a proprotein convertase subtilisin/kexin 9 inhibitor, which could be the future of lipid-lowering treatments and mipomersen would then likely be substituted. 

  • 226.
    Fernández Sjödin, Susana
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    I fotspåren av forskarnas jakt efter lösningen på gåtan: sambandet mellan narkolepsi och influensavaccinet Pandemrix2017Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
  • 227.
    Filipsson, Jessica
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Sömnbristens påverkan på den hormonella aptitregleringen: En systematisk litteraturstudie med metaanalys2019Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [sv]

    Bakgrund: Fetma har kommit att bli ett globalt problem, som ökar risken för såväl kardiovaskulära sjukdomar som cancer. Dessutom sover vi mindre idag, vilket korrelerar med fetma och ökad sjukdomsrisk. En normal aptitreglering följer vanligtvis en cirkadiansk rytm, likaså ett mönster efter en individs födointag. För lite sömn kan störa denna normala reglering, vilket i sin tur kan leda till ökad aptit och efterföljande ökat födointag.

    Syfte: Syftet var att undersöka befintlig forskning för att finna samband mellan sömnbrist och påverkan på den hormonella aptitregleringen hos vuxna människor, med fokus på de aptitreglerande hormonerna leptin och ghrelin.

    Metod: Studien var en systematisk litteraturstudie med metaanalys, där forskning söktes efter och granskades i databasen PubMed. Inklusions- och exklusionskriterier användes för att avgränsa studierna till de mest relevanta. Därefter applicerades datan i OpenMeta[Analyst] för att genomföra en metaanalys.

    Resultat: Sju studier inkluderades i litteraturstudien. Tre studier rapporterade en signifikant höjning av ghrelin vid sömnbrist, vilket inte gick att påvisa i en metaanalys. En studie rapporterade en signifikant höjning av leptin vid sömnbrist.

    Slutsats: Det gick inte att påvisa en signifikant skillnad i hormonnivåerna ghrelin eller leptin vid sömnbrist jämfört med normal sömn. Vidare studier är nödvändiga för att undersöka detta samband.

  • 228.
    Fischer, Benjamin
    et al.
    Fraunhofer Inst Biomed Engn, Germany.
    Meier, Anna
    Fraunhofer Inst Biomed Engn, Germany;Tech Univ Munich, Germany.
    Dehne, Annika
    Fraunhofer Inst Biomed Engn, Germany.
    Salhotra, Aseem
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences. Fraunhofer Inst Biomed Engn, Germany.
    Tran, Thao Anh
    Neumann, Sascha
    Fraunhofer Inst Biomed Engn, Germany;Univ Clin Essen, Germany.
    Schmidt, Katharina
    Fraunhofer Inst Biomed Engn, Germany.
    Meiser, Ina
    Fraunhofer Inst Biomed Engn, Germany.
    Neubauer, Julia C.
    Fraunhofer Inst Biomed Engn, Germany;Fraunhofer Project Ctr Stem Cell Proc Engn, Germany.
    Zimmermann, Heiko
    Fraunhofer Inst Biomed Engn, Germany;Fraunhofer Project Ctr Stem Cell Proc Engn, Germany;Saarland Univ, Germany;Univ Catolica Norte, Chile.
    Gentile, Luca
    Fraunhofer Inst Biomed Engn, Germany;Univ Appl Sci Kaiserslautern, Germany;Hasselt Univ, Belgium.
    A complete workflow for the differentiation and the dissociation of hiPSC-derived cardiospheres2018In: Stem Cell Research, ISSN 1873-5061, E-ISSN 1876-7753, Vol. 32, p. 65-72Article in journal (Refereed)
    Abstract [en]

    Cardiomyocytes derived from human induced pluripotent stem cells (hiPSC-CMs) are an invaluable tool for both basic and translational cardiovascular research. The potential that these cells hold for therapy, disease modeling and drug discovery is hampered by several bottlenecks that currently limit both the yield and the efficiency of cardiac induction. Here, we present a complete workflow for the production of ready-to-use hiPSC-CMs in a dynamic suspension bioreactor. This includes the efficient and highly reproducible differentiation of hiPSCs into cardiospheres, which display enhanced physiological maturation compared to static 3D induction in hanging drops, and a novel papain-based dissociation method that offers higher yield and viability than the broadly used dissociation reagents TrypLE and Accutase. Molecular and functional analyses of the cardiomyocytes reseeded after dissociation confirmed both the identity and the functionality of the cells, which can be used in down-stream applications, either as monolayers or spheroids.

  • 229.
    Fjällström, Ann-Kristin
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Signaling factors related to atrophy and hypertrophy in denervated skeletal muscle2014Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The human body consists of about 40 % skeletal muscles which control the body’s movement, ability to stand up, force generation, locomotion, heat production and are also the body’s protein reservoir. Muscle mass is controlled by the relationship between protein synthesis and protein degradation. Atrophy, a decrease in muscle mass, can be trigged by disuse, immobilization, inflammation and cancer. Hypertrophy, an increase in muscle mass, can occur after increased mechanical load, high usage and/or anabolic stimulation. The aim of this thesis was to investigate changes in expression and post translational modifications of some factors involved in the regulation of protein synthesis and protein degradation in 6-days denervated atrophic hind-limb muscles (anterior tibial and pooled gastrocnemius and soleus muscles) and in 6-days denervated hypertrophic hemidiaphragm muscle in mice. Protein expression and post translational modifications were studied semi-quantitatively using Western blots with whole muscle homogenates and separated nuclear and cytosolic fractions from both innervated and denervated muscles.  An increase in protein synthesis after denervation in both atrophic and hypertrophic muscles was suggested after studies of factors downstream of mTOR (paper I).  Other results suggest that FoxO1 and MuRF1 (paper II) participate in the tissue remodeling that occurs after denervation. A differential response of MK2 phosphorylation in denervated hypertrophic and atrophic muscles was confirmed (paper III). An increase in phosphorylation of the MK2 substrate Hsp 25 in all denervated muscles studied (paper III) indicates that other factors than MK2 are involved in regulating this phosphorylation. eIF4G phosphorylation at S1108 was investigated (paper IV) and a decrease was observed in atrophic muscle but an increase in hypertrophic muscle. The results in this thesis suggest that there are several factors that control protein degradation and protein synthesis in denervated atrophic and hypertrophic skeletal muscles. This is an intricate labyrinth with many different cell signaling factors, the function of which are still far from fully understood.

  • 230.
    Fjällström, Ann-Kristin
    et al.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Evertsson, Kim
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Norrby, Marlene
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Tågerud, Sven
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Forkhead box O1 and muscle RING finger 1protein expression in atrophic and hypertrophicdenervated mouse skeletal muscle2014In: Journal of Molecular Signaling, ISSN 1750-2187, E-ISSN 1750-2187, Vol. 9, article id 9Article in journal (Refereed)
    Abstract [en]

    Background: Forkhead box O (FoxO) transcription factors and E3 ubiquitin ligases such as Muscle RING finger 1 (MuRF1) are believed to participate in the regulation of skeletal muscle mass. The function of FoxO transcription factors is regulated by post-translational modifications such as phosphorylation and acetylation. In the present study FoxO1 protein expression, phosphorylation and acetylation as well as MuRF1 protein expression, were examined in atrophic and hypertrophic denervated skeletal muscle. Methods: Protein expression, phosphorylation and acetylation were studied semi-quantitatively using Western blots. Muscles studied were 6-days denervated mouse hind-limb muscles (anterior tibial as well as pooled gastrocnemius and soleus muscles, all atrophic), 6-days denervated mouse hemidiaphragm muscles (hypertrophic) and innervated control muscles. Total muscle homogenates were used as well as separated nuclear and cytosolic fractions of innervated and 6-days denervated anterior tibial and hemidiaphragm muscles. Results: Expression of FoxO1 and MuRF1 proteins increased 0.3-3.7-fold in all 6-days denervated muscles studied, atrophic as well as hypertrophic. Phosphorylation of FoxO1 at S256 increased about 0.8-1-fold after denervation in pooled gastrocnemius and soleus muscles and in hemidiaphragm but not in unfractionated anterior tibial muscle. A small (0.2-fold) but statistically significant increase in FoxO1 phosphorylation was, however, observed in cytosolic fractions of denervated anterior tibial muscle. A statistically significant increase in FoxO1 acetylation (0.8-fold) was observed only in denervated anterior tibial muscle. Increases in total FoxO1 and in phosphorylated FoxO1 were only seen in cytosolic fractions of denervated atrophic anterior tibial muscle whereas in denervated hypertrophic hemidiaphragm both total FoxO1 and phosphorylated FoxO1 increased in cytosolic as well as in nuclear fractions. MuRF1 protein expression increased in cytosolic as well as in nuclear fractions of both denervated atrophic anterior tibial muscle and denervated hypertrophic hemidiaphragm muscle. Conclusions: Increased expression of FoxO1 and MuRF1 in denervated muscles (atrophic as well as hypertrophic) suggests that these proteins participate in the tissue remodelling occurring after denervation. The effect of denervation on the level of phosphorylated and acetylated FoxO1 differed in the muscles studied and may be related to differences in fiber type composition of the muscles.

  • 231.
    Fjällström, Ann-Kristin
    et al.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Norrby, Marlene
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Tågerud, Sven
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Expression and phosphorylation of eukaryotic translation initiation factor 4-gamma (eIF4G) in denervated atrophic and hypertrophic mouse skeletal muscle2015In: Cell Biology International, ISSN 1065-6995, E-ISSN 1095-8355, Vol. 39, no 4, p. 496-501Article in journal (Refereed)
    Abstract [en]

    The eukaryotic translation initiation factor 4-gamma (eIF4G) is important for the initiation of protein synthesis and phosphorylation on S1108 regulates this function of eIF4G. Thus, increased phosphorylation has been reported in conditions associated with increased protein synthesis such as meal feeding and insulin/IGF-1 treatment whereas decreased phosphorylation occurs following starvation, dexamethasone treatment, in sepsis and in atrophic denervated hind-limb muscle. The aim of the present study was to test the hypothesis that S1108 phosphorylation of eIF4G is differentially affected in denervated atrophic hind-limb muscles and denervated hypertrophic hemidiaphragm muscle. Protein expression and phosphorylation in innervated and 6-days denervated atrophic hind-limb muscles (pooled gastrocnemius and soleus) and hypertrophic hemidiaphragms were studied semi-quantitatively using Western blots. Total expression of eIF4G did not change in denervated hind-limb muscles but increased about 77% in denervated hemidiaphragm. S1108 phosphorylated eIF4G decreased about 64% in denervated hind-limb muscles but increased about 1.3-fold in denervated hemidiaphragm. The ratio of S1108 phosphorylated eIF4G to total eIF4G decreased about 60% in denervated hind-limb muscles but no statistically significant change was observed in denervated hemidiaphragm. The differential effect of denervation on eIF4G expression and S1108 phosphorylation in hemidiaphragm (hypertrophic) and hind-limb muscle (atrophic) may represent a regulatory mechanism that helps clarify the differential response of these muscles following denervation.

  • 232.
    Flinkfeldt, Sofia
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    In-vitro studie av vichyvattens effekt mot Candida albicans2014Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    Introduction: Candida albicans is a dimorf, white fungus, which naturally colonises on skin and mucus membranes of humans. C. albicans is an opportunistic pathogen that often overgrows among patients with a compromised immunedefense. Oral overgrowth by C. albicans, oral candidosis, appears as white or grey lesions on the oral mucosa. This condition is common among infants and is then called ”thrush”. In the past, 0,1% crystal violet was used as treatment, but today the parents are recommended to brush soda water on the child’s oral mucosa. Nystatin is used as treatment in more serious infections.

    Objective: The aim of this study was to evaluate the effect of sodawaters, both with and without carbon dioxide, on a biofilm formed by C. albicans and on planctonic cells.

    Materials och methods: Five isolates of C. albicans were evaluated to determine which isolates formed the best biofilm. C. albicans isolates CCUG19915 and isolates C biofilms were exposed to different test solutions; sodawater (carbonated and non-carbonated), positive and negative controls for 10 minutes. This was followed by a crystal violet assay to quantify the remaining biofilm extent. A corresponding test with planktonic cells of C. albicans CCUG19915 was conducted.

    Results: No effect of sodawater, carbonated and non- carbonated, was detected on the biofilm. Cells exposed to crystal violet at the planktonic experiments formed much smaller colonies than the cells exposed to other test solutions. In one of two experiments a slight reduction in survival of cells exposed to crystal violet was noted.

    Discussion: The biofilm formation was similar among the isolates but isolates C and CCUG19915 were used for further analysis. The different results obtained with cells exposed to crystal violet, may be due to methodological errors e.g. that dilution was not done properly. The treatment recommendation of oral candidiasis in children is brushing the oral mucosa with sodawater. The effect may be caused by mechanical factors or the content of vichyvatten. Spontaneous healing of the candidiasis should not be overlooked.

    Conclusion: Soda water, carbonated and non- carbonated, had no effect on biofilms and gave no reduction in cell numbers that was statistically confirmed during the experiment with planctonic cells.

  • 233.
    Floberg, Malin
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Hjärtinsufficiens - Inblick i hur behandlingen i Sverige utvecklats sedan renässansen2018Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    Introduction: Heart failure is a condition where the heart’s pumping mechanism is reduced due to other heart diseases. Back in the days it was called dropsy (vattusot) and later it was called hydrops. The main reason for heart failure is often hypertension or a myocardial infarction with loss of heart muscle tissue.

    Heart failure can be divided into systolic- and diastolic heart failure. Systolic heart failure means that the heart is having trouble to pump out the blood in the left ventricle. In the case of diastolic heart failure, the heart is having trouble to fill with blood.

    Screening for heart failure is done by electrocardiography and measuring of natriuretic peptide. An ultrasound of the heart, so called echocardiography, is made to confirm the diagnosis. The echocardiography shows if the heart failure is systolic or diastolic.

    Symptoms of heart failure is shortness of breath, breathlessness and edema. Treatment of heart failure reduces the symptoms and the need for hospitalizing.

    Aim: The aim of this study was to explore if and how the treatment of heart failure has progressed in Sweden since the renaissance up to modern days.

    Method: Searches were made at libraries for books containing information about diseases in the old days and what the treatment looked like then. Suitable books where chosen to part the study. Information on current treatment was found at web pages such like läkemedelsboken.se and janusinfo.se.

    Results: The treatment of dropsy (vattusot) in the 1500s consisted mainly of various spices and plants that often were recommended to be sown in wine or other liquid before consumption. Digitoxin and digoxin, substances from digitalis, and diuretics were a big part of the treatment of heart failure in the 1800s and 1900s. There were multiple substances with diuretic effects which were recommended to use at hydrops and edema. Digitalis was found in many different formulations. Nowadays the use of digoxin as treatment for heart failure only occurs in more severe cases where todays standard treatment hasn’t given enough effect.

    Discussion and conclusion: The treatment of heart failure in Sweden has progressed since the renaissance as has the screening and naming of the condition. In the renaissance and 1800s the condition was called dropsy (vattusot), in the early 1900s it was called hydrops and it was called so until the middle of the 1900s, when it started to be called heart failure. From the premodern treatment, digoxin is the only substance used today only now its synthesized. Today’s standard treatment consists of ACE-inhibitors, beta blockers, diuretics and aldosterone antagonists. The books used in this study shows a progress in the treatment of heart failure.

  • 234.
    Forsberg, Eric
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Svaga syrors effekt på överlevnad och tillväxt: av mikroorganismer i såser2016Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    Trensums Food AB is a company that produces a wide variety of food products to different global trademark owners. Some of the products produced by Trensums Food AB are different kind of sauces, including BBQ-sauce and vanilla sauce. The sauce products are considered safe when an acid is added resulting in a pH < 4,2. The outsource of the company claims that it is important to use acetic acid instead of other kind of acids and that the pH is not crucial to consider the product safe. The goal of this project was to investigate how effectively different kind of organic acids work against microorganisms in the BBQ-sauce and milk-based sauce produced by Trensums Food AB. The main antimicrobial activity of an acid depends on its concentration of undissociated acid. Which further depends on the pKa-value of the acid and also the surrounding pH in the product. The pH was measured in the products to see if pH is critical for the antimicrobial activity or if the choice of acid is more important. The acids used in this project was acetic acid, citric acid and lactic acid and they were tested on Candida utilis, Bacillus subtilis and Enterococci faecium. BBQ-sauce and milk-based sauce were made in different batches containing 0, 0,12, 0,24 and 0,36 weight percent of respective acid. Each batch contained 103 CFU/ml of respective microorganism. After 5 days of incubation a viable count was performed. The acetic acid was the most effective acid in both type of sauces, reducing all microorganisms below the detection limit (< 101 CFU/ml) in the BBQ-sauce within all batches. The citric acid and lactic acid reduced only E.faecium and B.subtilis to a value below the lowest level of detection. In the milk-based sauce, which was contaminated with additional microorganisms, it was only the acetic acid that showed an increasing effect of antimicrobial activity with increasing concentration of acid. The pH was lower in the BBQ-sauce when using citric acid and lactic acid compared to when using acetic acid. Thus concluding that the antimicrobial activity of the selected microorganisms is not solely dependent on the level of pH but additionally the type of acid being used. The acetic acid has a higher pKa-value compared to the other acids and is therefore to a higher extent in a undissociated state. 

  • 235.
    Franco, Thiago A.
    et al.
    Univ Fed Rio de Janeiro, Brazil;Univ Calif Davis, USA.
    Xu, Pingxi
    Univ Calif Davis, USA.
    Brito, Nathalia F.
    Univ Fed Rio de Janeiro, Brazil.
    Oliveira, Daniele S.
    Univ Fed Rio de Janeiro, Brazil.
    Wen, Xiaolan
    Univ Calif Davis, USA.
    Moreira, Monica F.
    Univ Fed Rio de Janeiro, Brazil;Inst Nacl Ciencia & Tecnol Entomol Mol, Brazil.
    Unelius, C. Rikard
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Leal, Walter S.
    Univ Calif Davis, USA.
    Melo, Ana C. A.
    Univ Fed Rio de Janeiro, Brazil;Univ Calif Davis, USA;Inst Nacl Ciencia & Tecnol Entomol Mol, Brazil.
    Reverse chemical ecology-based approach leading to the accidental discovery of repellents for Rhodnius prolixus, a vector of Chagas diseases refractory to DEET2018In: Insect Biochemistry and Molecular Biology, ISSN 0965-1748, E-ISSN 1879-0240, Vol. 103, p. 46-52Article in journal (Refereed)
    Abstract [en]

    Rhodnius prolixus is one of the most important vectors of Chagas disease in Central and South America for which repellents and attractants are sorely needed. Repellents like DEET, picaridin, and IR3535 are widely used as the first line of defense against mosquitoes and other vectors, but they are ineffective against R. prolixus. Our initial goal was to identify in R. prolixus genome odorant receptors sensitive to putative sex pheromones. We compared gene expression of 21 ORs in the R. prolixus genome, identified 4 ORs enriched in male (compared with female) antennae. Attempts to de-orphanize these ORs using the Xenopus oocyte recording system showed that none of them responded to putative sex pheromone constituents. One of the them, RproOR80, was sensitive to 4 compounds in our panel of 109 odorants, namely, 2-heptanone, gamma-octalactone, acetophenone, and 4-methylcychohexanol. Interestingly, these compounds, particularly 4-methylcyclohexanol, showed strong repellency activity as indicated not only by a significant decrease in residence time close to a host, but also by a remarkable reduction in blood intake. 4-Methylcyclohexanol-elicited repellency activity was abolished in RNAi-treated insects. In summary, our search for pheromone receptors led to the discovery of repellents for R. prolixus.

  • 236.
    Fredriksson, Benjamin
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Effekt av ß-alanintillskott på Muskelkarnosin, Blodlaktat och Fysisk prestation.: En Litteraturstudie med Meta-analys2019Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    Background: The use of dietary supplements has increased in recent years. Which leads to the continuous production of new supplements that have no evidence of effect. A dietary supplement that has gained increased interest in recent years is β-alanine. For activities where glycolysis is stimulated and lactic acid production is high, β-alanine has been suggested to be an effective supplement. The effects and functions of ß-alanine in the body are not fully established. Purpose: The purpose of this study was to analyze the effects of ß-alanine supplementation on muscle carnosine concentration, blood lactate, muscle strength and endurance/time to exhaustion. Method: The study is designed as a systematic literature study with meta-analysis. Pubmed was used as a database for the literature search. Meta-assays were performed for carnosine concentration and blood lactate. Result: Dosage at 3.2g / day of β-alanine for 4 weeks shows significant effects on carnosine concentration. The size of the effect on carnosine concentration between the groups after 4 weeks of supplementation was 1,255 (p = 0.001). The effect size between the groups for 8-10 weeks was 2,054 (p = 0.008). No significant effects on blood lactate, the effect size between the groups was 0.148 (p = 0.278). Significant effect of βalanine on time to fatigue (TTE) in high intensity cycling. β-alanine supplementation showed significant effects on a repetition max (1RM) and whole body strength (WBS).

    2 Conclusion: β-alanine supplementation with a dosage of at least 3.2g / day for 4 weeks gives a significant increase in muscle carnosine concentration. Larger dosages than 3.2g does not show greater effect. β-alanine does not have a significant effect on blood lactate. Significant effect was shown on TTE for high intensity cycling sprints. The ßalanine supplemental effect on muscle strength is difficult to identify because only two studies could be included.

  • 237.
    Fredén, Caroline
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Rituximab som tilläggsbehandling till fludarabin och cyklofosfamid vid kronisk lymfatisk leukemi2016Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [sv]

    Kronisk lymfatisk leukemi (KLL) är en hematologisk malignitet som framför allt drabbar äldre personer. KLL går inte att bota men kan behandlas så att sjukdomen går i remission. Patienterna börjar behandlas när sjukdomssymtom förekommer. Det finns flera olika behandlingsalternativ. Vilken behandling som används beror bl.a. på patientens ålder och olika prognostiska faktorer.

    Syftet med arbetet var att utvärdera effekterna av rituximab som tillägg till fludarabin och cyklofosfamid (R-FC) vid behandling av KLL samt om behandlingen är kostnadseffektiv.

     Arbetet bestod av en litteraturstudie där fem vetenskapliga studier som hittats via sökningar i databasen PubMed valts ut för att besvara syftet. Av de utvalda studierna var det två randomiserade kliniska studier, två kohortstudier och en hälsoekonomisk studie.

     Resultaten från studierna visade att tilläggsbehandling med rituximab gav bättre behandlingseffekter både hos obehandlade patienter och hos patienter som behandlats tidigare. Den progressionsfria överlevnaden (PFS) blev signifikant längre med R-FC behandling. Även den totala överlevnaden blev längre och fler patienter uppnådde komplett remission. Studie 3 visade att minimal residual disease (MRD) nivån sänktes mer och hos fler av patienterna som fick R-FC. Låg MRD nivå gav också längre PFS. Studie 4 visade att patienter som hade ett högt uttryck av protein tyrosin kinas 2 (PTK2) genen och behandlades med R-FC hade längre PFS än de som fick FC. Den hälsoekonomiska studien visade att R-FC behandling höjde antalet kvalitetsjusterade levnadsår (QALY) med 1,127, kostnadseffektivitetskvoten (ICER) blev €17979 per QALY och behandlingen var kostnadseffektiv i Tyskland.

     Tillägg med rituximab gav signifikant bättre behandlingseffekter och är ett bra behandlingsalternativ framför allt hos de lite yngre patienterna som inte är så sjuka, som är jämförbara med patientpopulationen som deltog i studierna, medan det bl.a. beror på betalningsviljan per QALY om R-FC behandling är kostnadseffektiv även i Sverige.

  • 238.
    Frejd, Rebecka
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Vad är känt om Zikavirusets spridning, dess kliniska bild, patogenes, morfologi, diagnostik samt behandling?2017Independent thesis Basic level (university diploma), 10 credits / 15 HE creditsStudent thesis
    Abstract [sv]

    Zikaviruset är ett virus som fått stor uppmärksamhet i framför allt Sydamerika från 2015 och framåt då allt fler fall uppmärksammats. Detta arbete har utförts som en litteraturstudie med mål att sammanfatta kunskapsläget kring Zikavirusets morfologi, spridning, historia, komplikationer, diagnostik samt rådande behandlingsmöjligheter. Som källor används information från Folkhälsomyndigheten, CDC, PAHO och WHO samt MeSH-sökningar via PubMed.

    Viruset tillhör familjen Flaviviridae. Liknande andra virus i samma grupp kan infektionen ge feber, makulopapulösa hudutslag, konjunktivit, ledvärk, huvudvärk och myalgi. Det beskrevs först redan på slutet av 1940-talet i Afrika och har sedan rapporterats ha spridit sig till Asien, Oceanien, Stilla havsöarna och nu senast med utbrott i Sydamerika. Virusinfektionen har blivit mycket omdiskuterad då allt mer bevis kunnat läggas fram för att den kan leda till Guillain-Barrés syndrom samt även utöva teratogena effekter med mikrocefali som följd. Man har kartlagt spridning framför allt via myggarten Aedes men bevis finns även för att sexuell spridning kan ske samt att sjukdomen förefaller även kunna spridas från mor till foster. Diagnostiken baseras på RT-PCR och serologiska tester. I nuläget finns ingen aktiv behandling. Sammanfattningsvis har Zikavirus spridit sig snabbt genom Syd- och latinamerika sista åren och visat sig utgöra ett hot mot folkhälsan i dessa områden varför ett framtagande av ett fungerande vaccin är önskvärt.

  • 239.
    Fridlund, Jimmy
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Development of a Microbiological Method for Determining Serum Concentrations of Broad-spectrum β-lactam Antibiotics in Intensive Care Unit Patients2016Independent thesis Advanced level (degree of Master (Two Years)), 30 credits / 45 HE creditsStudent thesis
  • 240.
    Friedman, Ran
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Drug resistance in cancer: molecular evolution and compensatory proliferation2016In: OncoTarget, ISSN 1949-2553, E-ISSN 1949-2553, Vol. 7, no 11, p. 11746-11755Article in journal (Refereed)
    Abstract [en]

    Targeted therapies have revolutionized cancer treatment. Unfortunately, their success is limited due to the development of drug resistance within the tumor, which is an evolutionary process. Understanding how drug resistance evolves is a prerequisite to a better success of targeted therapies. Resistance is usually explained as a response to evolutionary pressure imposed by treatment. Thus, evolutionary understanding can and should be used in the design and treatment of cancer. In this article, drug-resistance to targeted therapies is reviewed from an evolutionary standpoint. The concept of apoptosis-induced compensatory proliferation (AICP) is developed. It is shown that AICP helps to explain some of the phenomena that are observed experimentally in cancers. Finally, potential drug targets are suggested in light of AICP.

  • 241.
    Friedman, Ran
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Drug Resistance Missense Mutations in Cancer Are Subject to Evolutionary Constraints2013In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 8, no 12, article id e82059Article in journal (Refereed)
    Abstract [en]

    Several tumor types are sensitive to deactivation of just one or very few genes that are constantly active in the cancer cells,a phenomenon that is termed oncogene addiction'. Drugs that target the products of those oncogenes can yield a temporary relief, and even complete remission. Unfortunately, many patients receiving oncogene-targeted therapies relapse on treatment. This often happens due to somatic mutations in the oncogene (resistance mutations"). 'Compound mutations', which in the context of cancer drug resistance are defined as two or more mutations of the drug target in the same clone may lead to enhanced resistance against the most selective inhibitors. Here, it is shown that the vast majority the resistance mutations occurring in cancer patients treated with tyrosin kinase inhibitors aimed at three different proteins follow an evolutionary pathway. Using bioinforrnatic analysis tools, found that the drug-resistance mutations in the tyrosine kinase domains of Abl1, ALK and exons 20 and 21 of EGFR favour transformations to residues that can be identified in similar positions in evolutionary related proteins. The results demonstrate that evolutionary pressure shapes the mutational landscape in the case of drug-resistance somatic mutations. The constraints on the mutational landscape suggest that it may be possible to counter single drug-resistance point mutations. The observation of relatively many resistance mutations in Abl1, but not in the other genes, is explained by the fact that mutations in Abl1 tend to be biochemically conservative, whereas mutations in EGFR and ALK tend to be radical. Analysis of Abl1 compound mutations suggests that such mutations are more prevalent than hitherto reported and may be more difficult to counter. This supports the notion that such mutations may provide an escape route for targeted cancer drug resistance.

  • 242.
    Friedman, Ran
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Electrolyte Solutions and Specific Ion Effects on Interfaces2013In: Journal of Chemical Education, ISSN 0021-9584, E-ISSN 1938-1328, Vol. 90, no 8, p. 1018-1023Article in journal (Refereed)
    Abstract [en]

    Introductory general and physical chemistry courses often deal with colligative properties of solutions and do not discuss nonideal solutions in detail. Yet, a growing body of evidence reveals that even at physiological concentrations electrolyte solutions cannot be treated as ideal when a charged or partially charged solute (such as a protein) is present in the solution. In such cases, the interactions between the salt ions and the solute depend on the specific ions that constitute the electrolyte solution (specific ion effects). For example, the catalytic efficiency of an enzyme may be different in NaCl and KCl solutions. In this article, specific ion effects are reviewed from a historical perspective, and then the current state of knowledge is presented at a qualitative level that is appropriate for second-year or advanced undergraduate science students. Finally, the related nomenclature (Bjerrum ion pairs, Hofmeister series, lyotropic series, and specific ion effects) is analyzed, and some suggestions are made with respect to the terminology, to make it more accessible to students. The material is appropriate for courses where solution chemistry is discussed, for example, in physical chemistry. In addition, it may be included in the chemistry curriculum for life or pharmaceutical sciences.

  • 243.
    Friedman, Ran
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Membrane-Ion Interactions2018In: Journal of Membrane Biology, ISSN 0022-2631, E-ISSN 1432-1424, Vol. 251, no 3, p. 453-460Article in journal (Refereed)
    Abstract [en]

    Biomembranes assemble and operate at the interface with electrolyte solutions. Interactions between ions in solutions and the lipid affect the membrane structure, dynamics and electrostatic potential. In this article, I review some of the experimental and computational methods that are used to study membrane-ions interactions. Experimental methods that account for membrane-ion interactions directly and indirectly are presented first. Then, studies in which molecular dynamics simulations were used to gain an understanding of membrane-ion interactions are surveyed. Finally, the current view on membrane-ion interactions and their significance is briefly discussed.

  • 244.
    Friedman, Ran
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Simulations of Biomolecules in Electrolyte Solutions2019In: Advanced Theory and Simulations, E-ISSN 2513-0390, Vol. 2, no 4, p. 1-10, article id 1800163Article in journal (Refereed)
    Abstract [en]

    Biomolecules including proteins, lipid membranes, and nucleic acids operate at an aqueous milieu that includes solvated ions. The interactions with ions affect biomolecules in different ways depending on the nature of the solute and the type of the ions. The dynamic nature of small soluble ions makes it difficult to follow them by structural methods. Consequently, theories were developed to explain how biomolecules interact in an environment that includes electrolytes. Moreover, simulations studies are often used to study such systems at the molecular or atomistic level. The status of the field, and inparticular of simulation studies, is the subject of this progress report.

  • 245.
    Friedman, Ran
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Specific Ion and Concentration Effects in Acetate Solutions with Na+, K+ and Cs+2019In: ChemPhysChem, ISSN 1439-4235, E-ISSN 1439-7641, Vol. 20, no 8, p. 1006-1010Article in journal (Refereed)
    Abstract [en]

    How salt ions affect solutes and the water beyond the solvation shell is not well understood. Molecular dynamics simulations of alkali-acetate solutions were analysed here in order to examine if, and how, different cations and solute concentrations affect the water structure and the interactions between water and acetates. The results revealed that water structure is perturbed to more than 1 nm away from the acetates and that this effect is more pronounced in physiological than in molar electrolyte concentrations. Analysis of simulations of a soluble protein revealed that the water orientation is perturbed to at least 1.5 nm from the protein structure. Furthermore, modifications to the orientation of water around carboxylate side chains were shown to depend on the local environment on the protein surface, and could extend to well over 1 nm, which may have an effect on protein dynamics during MD simulations in small water boxes.

  • 246.
    Friedman, Ran
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences. Ctr Biomat Chem.
    Structural and computational insights into the versatility of cadmium binding to proteins2014In: Dalton Transactions, ISSN 1477-9226, E-ISSN 1477-9234, Vol. 43, no 7, p. 2878-2887Article in journal (Refereed)
    Abstract [en]

    Cadmium is a highly toxic group XII metal, similar to zinc and mercury. Unlike zinc, which is one of the most common metal cofactors in biology, cadmium is highly toxic. Many Zn2+-binding proteins can bind Cd2+-ions without significantly affecting their structures. Here, the protein data bank is analysed with regard to protein-cadmium interactions, which shows that cadmium can bind to a variety of ion binding sites in proteins. Statistical analysis of Cd2+-side chain interactions is compared with a similar analysis of other ions. This analysis reveals that with regard to amino acid side-chain preference, Cd2+ is more similar to Mn2+ than to Zn2+ or Hg2+. Finally, the interaction energies of three native metal binding proteins are calculated where Cd2+ binds instead of Zn2+, Ca2+ or Cu2+. The interaction energies are decomposed into individual components whose contributions are discussed.

  • 247.
    Friedman, Ran
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    The molecular mechanism behind resistance of the kinase FLT3 to the inhibitor quizartinib2017In: Proteins: Structure, Function, and Bioinformatics, ISSN 0887-3585, E-ISSN 1097-0134, Vol. 85, no 11, p. 2143-2152Article in journal (Refereed)
    Abstract [en]

    Fms-like tyrosine kinase 3 (FLT3) is a receptor tyrosine kinase that is a drug target for leukemias. Several potent inhibitors of FLT3 exist, and bind to the inactive form of the enzyme. Unfortunately, resistance due to mutations in the kinase domain of FLT3 limits the therapeutic effects of these inhibitors. As in many other cases, it is not straightforward to explain why certain mutations lead to drug resistance. Extensive fully atomistic molecular dynamics (MD) simulations of FLT3 were carried out with an inhibited form (FLT-quizartinib complex), a free (apo) form, and an active conformation. In all cases, both the wild type (wt) proteins and two resistant mutants (D835F and Y842H) were studied. Analysis of the simulations revealed that impairment of protein-drug interactions cannot explain the resistance mutations in question. Rather, it appears that the active state of the mutant forms is perturbed by the mutations. It is therefore likely that perturbation of deactivation of the protein (which is necessary for drug binding) is responsible for the reduced affinity of the drug to the mutants. Importantly, this study suggests that it is possible to explain the source of resistance by mutations in FLT3 by an analysis of unbiased MD simulations.

  • 248.
    Friedman, Ran
    et al.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Agmon, Noam
    Hebrew Univ Jerusalem, Israel.
    Charge Transfer in Proteins: In Celebration of Hemi Gutman's 80th Birthday2017In: Israel Journal of Chemistry, ISSN 0021-2148, Vol. 57, no 5, p. 355-356Article in journal (Other academic)
  • 249.
    Friedman, Ran
    et al.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Boye, Kjetil
    Flatmark, Kjersti
    Molecular modelling and simulations in cancer research2013In: Biochimica et Biophysica Acta. CR. Reviews on Cancer, ISSN 0304-419X, E-ISSN 1879-2561, Vol. 1836, no 1, p. 1-14Article, review/survey (Refereed)
    Abstract [en]

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

  • 250.
    Friedman, Ran
    et al.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences. University of Zürich, Switzerland.
    Caflisch, Amedeo
    University of Zürich, Switzerland.
    Wild type and mutants of the HET-s(218-289) prion show different flexibility at fibrillar ends: A simulation study2014In: Proteins: Structure, Function, and Bioinformatics, ISSN 0887-3585, E-ISSN 1097-0134, Vol. 82, no 3, p. 399-404Article in journal (Refereed)
    Abstract [en]

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

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