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  • 1.
    Abada, Mariam
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Vilka problem finns det med förfalskade läkemedel?2014Independent thesis Basic level (university diploma), 10 credits / 15 HE creditsStudent thesis
    Abstract [sv]

    Världsmarknaden för läkemedlen beräknades år 2011 till 900 miljarder US$ enligt IMS-health. Marknaden för illegala läkemedel uppskattas vara värd mellan 75-200 miljarder dollar. I Sverige uppskattas den illegala läkemedelsmarknaden till motsvarande ≤0,5 %. Straffet för insmuggling av läkemedel till Sverige är böter eller max 2 års fängelse. Tullverket räknar med att man endast hittar 10 % av det som smugglas in. I andra länder kan straffet variera mellan böter (ekonomisk brottslighet i Afrika) till dödsstraff i Kina.

    I Utvecklingsländerna uppskattas 10-30 % av alla läkemedel som säljs vara förfalskade, jmf 1 % I-länderna. l. Förekomsten av förfalskade läkemedel har många allvarliga konsekvenser på människor som exempelvis, utebliven effekt, toxiska reaktioner, förgiftningar, som kan i värsta fall leda till döden. Ett annat alvarligt problem är resistensutveckling, ökad spridning av smittsamammasjukdomar som exempel, tuberkulos och/ eller HIV/AIDS.

    Syftet med detta examensarbete är att besvara frågan: Vilka problem ger den ökande förekomsten av förfalskade läkemedel i samhället. Undersökningen fokuserar på livstidsläkemedel, dvs ett läkemedel en person måste ta resten av sitt liv för behandling av sin kroniska sjukdom.

    För att komma till rätta med de problem, som förfalskade läkemedel, skapar krävs ett mer utvecklat samarbete mellan olika läkemedelsmyndigheter, läkemedelsföretag, internationella polisorganisationer, tull m.fl. Arbetet med att utveckla förpackningar som är svåra att förfalska bör intensifieras. Straffsatser bör kanske ses över. Det är viktigt att öka medvetandet bland allmänheten om risker med att köpa läkemedel utanför apotek (t ex via nätet).

  • 2.
    Abdo, Jasmin
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Tidig insulinbehandling för typ II diabetiker2016Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [sv]

    Diabetes mellitus är en av de vanligaste endokrina sjukdomarna och de vanligaste formerna är typ I och typ II. Idag har ca 350 000 personer i Sverige diabetes och av dessa har 85-90% diabetes typ II. Typ II diabetes börjar med insulinresistens och så småningom blir det avtagande funktion av β- cellerna vilket leder till nedsatt insulinkänslighet och främsta orsakerna till typ II diabetes är övervikt och fetma. Det finns olika behandlingsrekommendationer för att behandla typ II diabetiker för att minska att sena komplikationer uppstår. Främst genom livsstilsförändringar som kost och fysisk aktivitet, men då dessa inte räcker till kan perorala läkemedel komma i efterhand och om inte det heller ger tillräcklig effekt kan insulinbehandling sättas in. Ca 50 % av typ II diabetiker får insulin efter 10 års sjukdom.

    Syftet med arbetet är att undersöka om det finns en god implikation av att sätta in insulin tidigare än det som redan är rekommenderat.

    Denna litteraturstudie är baserad på artiklar hämtade från databasen PubMed. Sammanlagt har fem randomiserade kontrollerade studier granskats.

    Resultaten visar att en HbA1c-sänkning med ca 1,5 - 2,0 % kan erhållas samt också en bibehållen β- cellfunktion vid insättning av insulin. Insulinbehandlingen bör sättas in så snart HbA1c går över 7,5 % istället för att vänta en viss tid. Den kan sättas in hos behandlingsnaiva personer med framträdande symtom eftersom insulin fortfarande sänker HbA1c och det finns inget som tyder på att insulin inte kan sättas in tidigare än det som är rekommenderat.

    Slutsatsen som dras är att stödja intensiv behandling som gör att HbA1c hålls på en så låg nivå det är möjligt och när målvärden för HbA1c inte kan hållas kan insulin med fördel sättas in hos typ II diabetiker som behandlats med perorala antidiabetika.

  • 3.
    Abdulsalam Muhammednouri, Hevi
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Kan Entresto ersätta ACE-hämmare vid hjärtsvikt och är den behandlingen optimal med avseende på farmakogenetiken?2018Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    Around 200,000–250,000 people suffer from heart failure in Sweden. Heart failure is a condition of impaired heart pumping capacity. The condition results in reduced quality of life, high morbidity and mortality and there have been many attempts to find suitable drug targets to minimize these consequences. Neurohormonal compensatory mechanisms, such as renin–angiotensin–aldosterone system, aim to restore blood pressure to normal levels again but in the long-term it also increases the stress on the heart. The hormone angiotensin II gets activated through this mechanism and is the reason behind the increased stress. Therefore, the hormone has been an important drug target for ACE inhibitors (ACEI) and AT1 blockers (ARB) to prevent antihypertensive effects. The enzyme neprilysin is another drug target whose inhibition is accomplished by using neprilysin inhibitors. Entresto® is a new medication that contains a neprilysin inhibitor and an ARB. The neprilysin inhibitory component, sacubitril, is activated by carboxylesterase 1 (CES1) but mutations in the gene encoding CES1 may cause a non-therapeutic effect. Additionally, patients with wild-type CES1 may risk unacceptable side effects such as rhabdomyolysis and Alzheimer's disease. The objective of this study is to investigate whether replacement of ACE inhibitors with Entresto is optimal in heart failure with regard to pharmacogenetics.

    This study is organized as a literature study in which five scientific articles (I-V) were analyzed and selected from PubMed database and through Linnaeus University's search engine, OneSearch. The studies show that Entresto is superior to enalapril in reducing the risk for cardiovascular death or hospitalization for heart failure. However, the effects of Entresto is dependent on a functioning CES1 gene because mutations like G143E cause a non-therapeutic effect. Enalapril has shown to be independent of such mutations.

    Theoretically, inhibition of neprilysin may cause accumulation of amyloid-β peptides (Aβ), which associates with Alzheimer's disease. Study IV, with the purpose to investigate the effect of Entresto on Aβ isoforms, showed no significant change in Aβ concentrations in cerebrospinal fluid. However, further studies with longer duration were suggested. On the other hand, study V shows that a combination of Entresto and statins increases the plasma concentration of statins. That in turn would increase the risk of a development of rhabdomyolysis. The conclusion is that it is not optimal to replace enalapril with Entresto in heart failure with regard to pharmacogenetics.

  • 4.
    Abiib, Amina
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Probiotika som behandling vid IBS2016Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    Background: IBS (Irritable Bowel Syndrome) is a functional gastrointestinal disorder, with an unclear etiology and pathophysiology. IBS is a common disorder in the Western population and is characterized by recurrent abdominal pain/ discomfort, bloating, flatulence, diarrhea and/ or constipation. There is currently no cure for IBS, but the interest in probiotics as an option of treatment has recently increased. Probiotics have been defined as live microorganisms that, when administered in adequate amounts, provide a health benefit on the host, and are believed to have a symptomatic effect in IBS. Probiotics have therefore been of interest for the treatment in IBS.

    Purpose: The purpose of this study is to examine whether probiotics have a therapeutic effect and if it could be used as a treatment for IBS.

    Method: Five randomized, double-blind, placebo-controlled studies were reviewed that examined the therapeutic effect of different probiotics in the IBS-patients. Articles were obtained through searches in the medical database PubMed, during the month of February 2016.

    Results: Four of the five studies showed a significant improvement of symptoms especially in abdominal pain/ discomfort. The best results were seen in a study that investigated the probiotic Lactobacillus plantarum 299v. Three of the five studies showed a significant improvement in quality of life (QOL) of the subjects in the study. One of the five studies which examined the effect of Escherichia coli Nissle 1917, there was no significant difference between E.coli (probiotics) and placebo.

    Conclusion: There is reasonable evidence that treatment with certain probiotics might provide improvement in symptoms of abdominal pain/ discomfort, and increase patients quality of life based on the five studies. Further studies are required to determine the most effective probiotic, dose and duration of IBS-treatment.

  • 5.
    Adel Ali, Sura
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Kan manuell analys av Csv-EPK ersättas med automatiserad analys på Sysmex XN-1000?2016Independent thesis Basic level (degree of Bachelor), 180 HE creditsStudent thesis
    Abstract [en]

    Determination of erythrocyte count in cerebrospinal fluid (CSF-EPC) is used to exclude various intracranial hemorrhage, especially subarachnoid hemorrhage (SAH). SAH means a bleeding between the pia mater and arachnoidea which occurs due to rupture of an aneurysm in the subarachnoid space. Manual counting of erythrocytes in the cerebrospinal fluid with Bürkers chamber and microscopy has been the gold standard for the past decades, but the manual method is time consuming and requires great experience. The purpose of this study was to evaluate if manual analysis of  CSF-EPC with counting chamber, and light microscopy can be replaced by automated analysis of CSF-EPC with Hematology Analyzer XN-1000 (Sysmex). Fortyeight cerebrospinal fluid samples with various concentrations of erythrocytes ware prepared by diluting known concentration of erythrocytes in cell-free CSF. Prepared CSF-samples with added erythrocytes were analyzed first on the XN-1000. Thereafter, manual counting of erythrocytes was performed using Bürkers counting chamber. A linear regression was established to describe the correlation between the automated analysis of the CSF-EPC and manual analysis of the CSF-EPC. Imprecision in the analysis of the CSF-EPC on the XN-1000 (Sysmex) was assessed by within-run imprecision. A very good correlation (r = 0.999) was found between the XN-1000 and manual counting. For results in the lower range, 100 - 5000 (106/L), correlation was also good (r = 0.997). The coefficient of variation was 19,8 % at CSF-EPC of 370 x 106/L and 3.1 % at CSF-EPC of 25 950 x 106/L. The sensitivity for analysis of CSF-EPC on XN-1000 was 370 x 106/L. The conclusion is that the analysis of Csv-EPC on XN-1000 can be used for clinical diagnostics of CSF- samples. However, it should be noted that XN-1000 has poor sensitivity for low CSF-EPC values < 370 x 106/L. To ensure high diagnostic quality even in CSF-samples with low erythrocyte counts are recommended a reference limit of < 500 x 106/L as a practical cut off for supplemental microscopic counting in routine healthcare laboratories.

     

     

     

  • 6.
    Adell, Jenny
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Isolering och identifiering av bakterie som orsakar missfärgning på kött2017Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    Meat is skeletal muscle from different animals, such as pigs, cattle or sheep. Pseudomonas are bacteria that may cause food spoilage. The bacteria live in our environment and can cause problems due to biofilm formation in hospitals and industries. The slaughterhouse KLS Ugglarps has found that some pig cuttings have become discolored with at blue color and they wanted to find out what caused it. Pseudomonas aeruginosa had previously been found in the production area and was suspected as the cause.Meat, with and without discoloration, was investigated using various microbiological methods to see which bacterium cause the blue color. Different colonies were isolated and identified. The methods used were API 20NE, gram staining and oxidation test. A reference isolate was used as control. It was found that it was not P. aeruginosa but instead Pseudomonas fluorescens that caused the blue color. This was confirmed by applying the isolated bacteria to sterile meat and the blue color did appear after incubation. A screening for the source of contamination was performed in the production area to see if the bacterium could be found before start-up and during production. The samples taken showed that there were bacteria at both time points and that the production surfaces at the beginning of the production line were more prone to contamination than the other surfaces.

  • 7.
    Adler, Anna
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Är det säkert att byta från originalläkemedlet för inflixmab, Remicade®, till CT-P13 och är CT-P13 ekvivalent med Remicade® med avseende på effekt, säkerhet, immunogenicitet och farmakokinetik?2016Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    Biologic drugs are effective against numerous diseases but they are very expensive. The European Medicines Agency approved sales of biosimilars in 2006. Biosimilars are copies of already approved biologic drugs, but they are not considered to be exact copies like generic drugs are. Only living organisms can produce substances with the complexity of biologic drugs. Differences in pH, enviroment, and the purification process during the production of biologic drugs can affect the structure of the final product. Differences in the production processes can affect properties like the glycosylation pattern of the molecules which in turn can influence the effect of the drug. This is the reason biosimilars are not considered as exact copies of the original drug. The patent for Remicade® a TNF inhibitor expired in 2015 which led to the introduction of the first biosimilar for monoclonal antibodies (CT-P13) on the European market. The aim of this study was to investigate the efficacy, safety profile, immunogenicity and pharmacokinetics equivalence between CT-P13 and the original drug for infliximab, Remicade®. And to investigate if it was safe to switch from Remicade to CT-P13.

     

    The articles for the study were collected from PubMed, a medical and bioscientific database, and five studies were chosen for further analysis. The articles were not limited to a specific indication for infliximab, so the studies included patients with rhematoid arthritis (RA), ankylosing spondylitis (AS) and inflammatory bowel disease (IBD). The short-term equivalence between Remicade® and CT-P13 was analysed in the studies but more studies including long-term equivalence are needed. Based on the primary endpoints in the studies it seems to be safe to switch from Remicade® to CT-P13 and short-term equivalence seems to exist between CT-P13 and Remicade® considering the efficacy, safety profile, immunogenicity and pharmacokinetics equivalence in patients with RA, AS and IBD.

  • 8.
    Adolfsson, Matilda
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Anthelmintika mot hästens inälvsparasiter: en studie av effekt, resistensförekomst och försäljning2016Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
  • 9.
    Aeinehband, Shahin
    et al.
    Karolinska Institutet.
    Lindblom, Rickard P. F.
    Karolinska Institutet.
    Al Nimer, Faiez
    Karolinska Institutet.
    Vijayaraghavan, Swetha
    Karolinska Institutet.
    Sandholm, Kerstin
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Khademi, Mohsen
    Karolinska Institutet.
    Olsson, Tomas
    Karolinska Institutet.
    Nilsson, Bo
    Uppsala University.
    Nilsson Ekdahl, Kristina
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences. Uppsala University.
    Darreh-Shori, Taher
    Karolinska Institutet.
    Piehl, Fredrik
    Karolinska Institutet.
    Complement Component C3 and Butyrylcholinesterase Activity Are Associated with Neurodegeneration and Clinical Disability in Multiple Sclerosis2015In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 10, no 4, article id e0122048Article in journal (Refereed)
    Abstract [en]

    Dysregulation of the complement system is evident in many CNS diseases but mechanisms regulating complement activation in the CNS remain unclear. In a recent large rat genomewide expression profiling and linkage analysis we found co-regulation of complement C3 immediately downstream of butyrylcholinesterase (BuChE), an enzyme hydrolyzing acetylcholine (ACh), a classical neurotransmitter with immunoregulatory effects. We here determined levels of neurofilament-light (NFL), a marker for ongoing nerve injury, C3 and activity of the two main ACh hydrolyzing enzymes, acetylcholinesterase (AChE) and BuChE, in cerebrospinal fluid (CSF) from patients with MS (n = 48) and non-inflammatory controls (n = 18). C3 levels were elevated in MS patients compared to controls and correlated both to disability and NFL. C3 levels were not induced by relapses, but were increased in patients with >= 9 cerebral lesions on magnetic resonance imaging and in patients with progressive disease. BuChE activity did not differ at the group level, but was correlated to both C3 and NFL levels in individual samples. In conclusion, we show that CSF C3 correlates both to a marker for ongoing nerve injury and degree of disease disability. Moreover, our results also suggest a potential link between intrathecal cholinergic activity and complement activation. These results motivate further efforts directed at elucidating the regulation and effector functions of the complement system in MS, and its relation to cholinergic tone.

  • 10.
    Agell, Blenda
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Effect of Antibacterial Mouthwash on Basal Metabolic Rate in Humans: A Randomized, Double-blinded, Cross-over Study2013Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    The use of mouthwash is a common complement to oral care. However, the physiological implication of this use, besides of effects on oral hygiene, is poorly known. The research of the gut micro flora and its implications on the host is a very active area of research today. Many important connections between the gut micro flora and obesity and diabetes have been found. These billions of bacteria are part of the immune system, they produce essential vitamins and they make inaccessible polysaccharides more digestible to the host, just to mention a few of their symbiotic roles for the host.

    A less explored area is the micro flora in the oral cavity. On the back of the tongue, anaerobic bacteria can reduce dietary nitrate to nitrite which then further can be reduced to nitric oxide, NO. NO is important in several important biological functions, e.g. as a signal substance, vasoregulation, mucus production and antibacterial effects. Vegetables as beetroot and spinach are dietary sources with a high nitrate content. Also drinking water and processed meats can be of relevance. Nitrite is added to processed meat for the prevention of botulism but also adds taste and color.  

    Experiments on humans indicate that mitochondrial efficiency increases after nitrate load, manifested as a decreased oxygen demand during physical exercise. This can also be relevant under conditions where the mitochondrial function is impaired, such as in diabetes and cardiovascular diseases.

    First a pilot study was made to evaluate the nitrate reducing effect from the antibacterial mouthwash. The mouthwash proved very effective. The concentrations of nitrate and nitrite in saliva was analyzed by HPLC and saliva from the antibacterial treatment showed greatly reduced concentrations of nitrite and high concentrations of nitrate. Saliva from placebo mouthwash showed high concentrations of nitrite and low concentrations of nitrate as expected.

    To study the importance of oral bacteria on metabolism, we performed a randomized, cross-over double-blinded study with 19 healthy males between 22-43 years. During two separate three-day periods they used an antibacterial and placebo mouthwash, respectively. On the fourth day their basal metabolic rate (BMR) was measured with an indirect calorimetric system. Moreover, samples from saliva, urine and blood were collected but these results are not included in this thesis. An earlier, unpublished study has demonstrated that nitrate administration reduces the basal metabolic rate. Accordingly, our aim was to study potential effects on the basal metabolic rate following reduction of the number of oral bacteria by aid of antibacterial mouthwash. Our hypothesis was that the reduced availability of nitrite would decrease the availability of NO in the body and manifest as an increased basal metabolic rate.

    The results from indirect calorimetry measurements showed no significant difference between placebo and antibacterial mouthwash, but there may be confounding factors. Further study is needed to assess the potential effects on host metabolism by these bacteria.

  • 11.
    Ahlin, Ellen
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Utvärdering av dricksvattenkvaliteten i Bjuv: Kartläggning av klagomål och eftersökning av orsak2013Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [sv]

    Vid bytet från grundvattentäkt till ytvattentäkt i Bjuvs kommun började klagomål om dricksvattnets kvalitet att strömma in till Nordvästra Skånes Vatten och Avlopp (NSVA), ansvarig för vattenverksamheten i kommunen. Syftet med denna studie är att kartlägga klagomålen kring dricksvattnet, ringa in problemet och eftersöka orsaken. Detta har skett genom intervjuer med konsumenter liksom vattenprovtagningar hos dessa. En geografisk spridning låg till grund vid valet av provtagningspunkterna. Utöver mikrobiologiska, kemiska och fysikaliska parametrar som inkluderas i Livsmedelsverkets föreskrifter om dricksvatten har vattnet analyserats för innehåll av geosmin, 2-metylisoborneol och 2,4,6-trikloranisol då dessa föreningar är kända för att orsaka dålig lukt och bismak på dricksvatten. Analysresultaten visar generellt på ett vatten med god kvalitet. Av de intervjuer som gjorts hos de utvalda konsumenterna framgår det dock att vattenkvaliteten inte är tillfredsställande. Det är i huvudsak vattnets lukt och smak som kritiseras där unken och mögel är den vanligaste beskrivningen. Vad denna lukt och smak beror på har inte kunnat fastställas. En kartläggning av klagomålen och definiering av problemet har dock påbörjats vilket underlättar för fortsatta studier och eventuella åtgärder.

  • 12.
    Ahlstrand, Emma
    et al.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Buetti-Dinh, Antoine
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences. Universita’ della Svizzera Italiana, Switzerland;Swiss Institute of Bioinformatics, Switzerland.
    Friedman, Ran
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    An interactive computer lab of the galvanic cell for students in biochemistry2018In: Biochemistry and molecular biology education, ISSN 1470-8175, E-ISSN 1539-3429, Vol. 46, no 1, p. 58-65Article in journal (Refereed)
    Abstract [en]

    We describe an interactive module that can be used to teach basic concepts in electrochemistry and thermodynamics to first year natural science students. The module is used together with an experimental laboratory and improves the students’ understanding of thermodynamic quantities such as ΔrG, ΔrH, and ΔrS that are calculated but not directly measured in the lab. We also discuss how new technologies can substitute some parts of experimental chemistry courses, and improve accessibility to course material. Cloud computing platforms such as CoCalc facilitate the distribution of computer codes and allow students to access and apply interactive course tools beyond the course's scope. Despite some limitations imposed by cloud computing, the students appreciated the approach and the enhanced opportunities to discuss study questions with their classmates and instructor as facilitated by the interactive tools. 

  • 13.
    Ahlstrand, Emma
    et al.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Hermansson, Kersti
    Uppsala University.
    Friedman, Ran
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Interaction Energies in Complexes of Zn and Amino Acids: A Comparison of Ab Initio and Force Field Based Calculations2017In: Journal of Physical Chemistry A, ISSN 1089-5639, E-ISSN 1520-5215, Vol. 121, no 13, p. 2643-2654Article in journal (Refereed)
    Abstract [en]

    Zinc plays important roles in structural stabilization of proteins, eniyine catalysis, and signal transduction. Many Zn binding sites are located at the interface between the protein and the cellular fluid. In aqueous solutions, Zn ions adopt an octahedral coordination, while in proteins zinc can have different coordinations, with a tetrahedral conformation found most frequently. The dynainics of Zn binding to proteins and the formation of complexes that involve Zn are dictated by interactions between Zn and its binding partners. We calculated the interaction energies between Zn and its ligands in complexes that mimic protein binding sites and in Zn complexes of water and one or two amino acid moieties, using quantum mechanics (QM) and molecular mechanics (MM). It was found that MM calculations that neglect or only approximate polarizability did not reproduce even the relative order of the QM interaction energies in these complexes. Interaction energies calculated with the CHARMM-Diode polarizable force field agreed better with the ab initio results,:although the deviations between QM and MM were still rather large (40-96 kcallmol). In order to gain further insight into Zn ligand interactions, the free energies of interaction were estimated by QM calculations with continuum solvent representation, and we performed energy decomposition analysis calculations to examine the characteristics of the different complexes. The ligand-types were found to have high impact on the relative strength of polarization and electrostatic interactions. Interestingly, ligand ligand interactions did not play a significant role in the binding of Zn. Finally) analysis of ligand exchange energies suggests that carboxylates could be exchanged with water molecules, which explains the flexibility in Zn:binding dynamics. An exchange between earboxylate (Asp/Glii) and imidazole (His) is less likely.

  • 14.
    Ahlstrand, Emma
    et al.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Spångberg, Daniel
    Uppsala University.
    Hermansson, Kersti
    Uppsala University.
    Friedman, Ran
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Interaction energies between metal ions (Zn2+ and Cd2+) and biologically relevant ligands2013In: International Journal of Quantum Chemistry, ISSN 0020-7608, E-ISSN 1097-461X, Vol. 113, no 23, p. 2554-2562Article in journal (Refereed)
    Abstract [en]

    Interactions between the group XII metals Zn2+ and Cd2+ and amino acid residues play an important role in biology due to the prevalence of the first and the toxicity of the second. Estimates of the interaction energies between the ions and relevant residues in proteins are however difficult to obtain. This study reports on calculated interaction energy curves for small complexes of Zn2+ or Cd2+ and amino acid mimics (acetate, methanethiolate, and imidazole) or water. Given that many applications and models (e.g., force fields, solvation models, etc.) begin with and rely on an accurate description of gas-phase interaction energies, this is where our focus lies in this study. Four density functional theory (DFT)-functionals and MP2 were used to calculate the interaction energies not only at the respective equilibrium distances but also at a relevant range of ion–ligand separation distances. The calculated values were compared with those obtained by CCSD(T). All DFT-methods are found to overestimate the magnitude of the interaction energy compared to the CCSD(T) reference values. The deviation was analyzed in terms of energy components from localized molecular orbital energy decomposition analysis scheme and is mostly attributed to overestimation of the polarization energy. MP2 shows good agreement with CCSD(T) [root mean square error (RMSE) = 1.2 kcal/mol] for the eight studied complexes at equilibrium distance. Dispersion energy differences at longer separation give rise to increased deviations between MP2 and CCSD(T) (RMSE = 6.4 kcal/mol at 3.0 Å). Overall, the results call for caution in applying DFT methods to metalloprotein model complexes even with closed-shell metal ions such as Zn2+ and Cd2+, in particular at ion–ligand separations that are longer than the equilibrium distances.

  • 15.
    Ahlstrand, Emma
    et al.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Zukerman Schpector, Julio
    Universidade Federal de São Carlos, Brazil.
    Friedman, Ran
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Computer simulations of alkali-acetate solutions: Accuracy of the forcefields in difference concentrations2017In: Journal of Chemical Physics, ISSN 0021-9606, E-ISSN 1089-7690, Vol. 147, p. 1-10, article id 194102Article in journal (Refereed)
    Abstract [en]

    When proteins are solvated in electrolyte solutions that contain alkali ions, the ions interact mostlywith carboxylates on the protein surface. Correctly accounting for alkali-carboxylate interactionsis thus important for realistic simulations of proteins. Acetates are the simplest carboxylates thatare amphipathic, and experimental data for alkali acetate solutions are available and can be comparedwith observables obtained from simulations. We carried out molecular dynamics simulations of alkali acetate solutions using polarizable and non-polarizable forcefields and examined the ionacetateinteractions. In particular, activity coefficients and association constants were studied in a range of concentrations (0.03, 0.1, and 1M). In addition, quantum-mechanics (QM) based energy decomposition analysis was performed in order to estimate the contribution of polarization, electrostatics, dispersion, and QM (non-classical) effects on the cation-acetate and cation-water interactions. Simulations of Li-acetate solutions in general overestimated the binding of Li+ and acetates. In lower concentrations, the activity coefficients of alkali-acetate solutions were too high, which is suggested to be due to the simulation protocol and not the forcefields. Energy decomposition analysis suggested that improvement of the forcefield parameters to enable accurate simulations of Li-acetate solution scan be achieved but may require the use of a polarizable forcefield. Importantly, simulations with some ion parameters could not reproduce the correct ion-oxygen distances, which calls for caution in thechoice of ion parameters when protein simulations are performed in electrolyte solutions.

  • 16.
    Al-Asafi, Zainab
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Förekomst av Mycobacterium avium i vattenprover från barns närmiljö: med fokus på badleksaker2015Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    Mycobacteria are gram-positive bacteria belonging to the Mycobacteriaceae family. There are more than 50 different species of the mycobacteria which can cause diseases in humans, the most important one being M. tuberculosis. Non-tuberculous mycobacteria are also called environmental mycobacteria. Some species can survive in areas with very low amounts of nutrients along with aquatic areas, such as water, dirt, swamps, and marshes. Some environmental mycobacteria are pathogenic and can cause diseases in humans and animals. They are mostly opportunistic pathogens, i.e. they infect humans with an already weakened immune system or humans who suffer from chronic diseases. Two species of mycobacteria named Mycobacterium avium avium and Mycobacterium avium hominissuis belong to the subgroup Mycobacterium avium complex (MAC). Healthy children between the ages of 1 and 5 are an exposed group to MAC-infections. When these children are infected with MAC, they develop an inflammation in the lymph nodes (Lymphadenitis) in the neck area. Since no direct transmission between humans has been established, it has been speculated that the MAC-bacteria take a different route to reach and infect adults and children with lymphadenitis. It has been hypothesized that MAC infect humans through nature and drinking water.

    The purpose of this study was to develop a method to detect the occurrence of M. avium bacteria in tap water from Öland, Kalmar, and Hultsfred, incubated in rubber ducks. The purpose was also to investigate experimentally if M. avium can survive and/or thrive in a rubber duck environment. The methods which have been evaluated in the study were cultivation followed by detection by MALDI-TOF and also triplex q-PCR.  

    The study was done on clean (new) and contaminated (used) rubber ducks with tap water from Öland, Kalmar, and Hultsfred, where some rubber ducks were injected with known strains from M. avium avium and M. avium hominissuis and incubated for five weeks. DNA was extracted from the water and biofilm samples from each rubber duck, for further analysis with q-PCR. Furthermore, a culture from the same water samples was made on nutritious agar for later detection by MALDI-TOF.

    The results of this study using q-PCR showed detection of the bacteria M. avium avium and M. avium hominissuis in all the samples. A possible, and believable, reason for this could be that the extraction solutions used in this study were contaminated. However, the study show that the mycobacteria survive in rubber duck environment.

  • 17.
    Aldén, Erik
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Livsstilsförändringar vid fetma: En litteraturstudie som undersöker livsstilsförändringar samt hur täta kontakter påverkar följsamheten2018Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    Background: Obesity has become one of our times most endemic disease on a global scale and changes to lifestyle is the most cost-effective way to treat patients, when the cost for healthcare related treatment is staggeringly high for obesity and sequela diseases NAFLD, diabetes typ 2, dyslipidaemia and metabolic syndrome.The problem with this remedy is that it requires work and dedication. But changes require hard work, and in this patient group- low compliance, weight gain after treatment, dropping out of programs and small desire to change are the most common problems. Motivational studies report that readiness in obese patients is low and the best way to help patients to move forward is by motivational conversations. The obesity sequela disease NAFLD is an asymptomatic disease it displays no symptoms until very late stages. Therefore it’s a problem to get patients make the patient understand his illness and the seriousness of it.

    Aim: This literature work was aimed at investigating compliance in lifestyle changes in obese subject and to see if close contact with healthcare staff affected the achieved results.

    Method: In this literature study, the databases Pubmed, Science Direct, Medline and Sportdiscus were used to find information. Article inclusion criteria were that the articles were not older than 10 years and were in English.

    Result: Frequent and regular contacts between participants and professional staff provided good results both with regard to weight loss, biochemical response, and the participants' willingness to change. Also it shows that return visits at least every three months will improve weight loss if the participant is motivated to implement a change to lifestyle.

    Conclusion: Overall, this literature study shows the difficulties with lifestyle changes in people with obesity and sequela NAFLD. Close contacts of the patients with healthcare staff has proven to have a positive impact on treatment compliance, but there are other lifestyle difficulties in these patient groups which hamper compliance. 

  • 18.
    Alexandersson, Sandra
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Akutpreventivmedel: Hur skiljer sig effektivitet och säkerhet för de tre godkända metoderna levonorgestrel, ulipristal och kopparspiral?2014Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [sv]

    I Sverige är abort en laglig rättighet och det finns flera godkända metoder för regelbunden antikonception. Ändå finns ett behov av akutmetoder för att förhindra oönskad graviditet.  Det finns tre godkända akutpreventivmedelsmetoder; levonorgestrel, ulipristal och kopparspiral. Detta arbetes syfte var att undersöka effektivitet och säkerhet för dessa tre godkända metoder. En litteratursökning gjordes i databasen PubMed,  7 artiklar valdes ut för analys. Artikel 1och 2 undersökte levonorgestrels effektivitet och säkerhet och kunde redovisa graviditetsfrekvenser på 0, 57%  och 0,67 % , samt en graviditetsförebyggande effektivitet på 68 %. Artikel 3 jämförde ulipristal och levonorgestrel och redovisade graviditetsfrekvenser på 1,8 % för ulipristal och 2,6 % för levonorgestrel. Även ”non-inferiority” konstaterades med OR på 0,68. Artikel 4 undersökte levonorgestrels effektivitet och redovisade graviditetsfrekvenser på 2,0 % (12 h- gruppen) och 1,9 % (24 h- gruppen), dessutom redovisades en graviditetsförebyggande effektivitet på 72 % (12 h- gruppen) och 75 % (24 h- gruppen). Artikel 5 jämförde ulipristal och levonorgestrel och fann att ulipristalbehandling  är ”non-inferiority” till levonorgestrelbehandling. Artikel 6 undersökte ulipristals effektivitet och redovisade en graviditetsfrekvens på 2, 1 % och en graviditetsförebyggande effektivitet på  62, 3%. Artikel 7 undersökte kopparspiralens effektivitet och kunde redovisa 100 % graviditetsförebyggande effektivitet. Akutpreventivmedel fungerar inte alltid, men förhindrar oönskade graviditeter. Slutsatsen är att resultaten ger stöd för gällande behandlingsrekommendationer.

  • 19.
    Ali Ghani, Hawraa
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Funktionella studier av VEGFR2-bindande affibody-molekyler kovalent konjugerade till spindelsilke2018Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    Spider silk and its mechanical properties are today well-recognized. Obtaining sufficient amount of spider silk from spiders is complicated, therefore a method to produce recombinant spider silk fusion protein (4RepCT) has been developed. 4RepCT has biocompatible properties and can be used as a scaffold for cell cultures. Fibronectin, (FN) is a glycoprotein found in the extracellular matrix containing peptides that stimulate cell adherence. 4RepCT can be genetically coupled to a FN-peptide (FN-4RepCT). The vascular endothelial growth factor receptor-2 (VEGFR-2) is found on endothelial cell which are activated by VEGF-polypeptides. This initiates growth of existing blood vessels which can be observed in cancerous diseases and therefore VEGFR-2 is an attractive and promising target in cancer research. During this study transgenic cells that overexpress VEGFR-2, 293/KDR were used.

    The aim of the study is to examine the functionality and bioactivity of VEGFR-2-binding affibody molecules after their conjugation with 4RepCT and FN-4RepCT.

    Alamar Blue and the biochemical assay ELISA were used to examine cell proliferation/viability and phosphorylation respectively. Cell proliferation of 293/KDR was analyzed in wells coated initially with 4RepCT followed by one extra coating of the following affibody molecules: Zdimer-4RepCT, Ztetramer-4RepCT, FN-4RepCT, ZDimer-FN, Ztetramer-FN-4RepCT and 4RepCT. Phosphorylation was examined of 293/KDRs VEGFR-2 cultures on the mentioned coatings using ELISA.

    293/KDRs highest proliferation value was obtained on Ztetramer-FN-4RepCT. Zdimer-FN-4RepCT had a lower cell proliferation than Ztetramer-FN-4RepCT. The phosphorylation results showed that the affibody-molecule Ztetramer-4RepCT has a stronger effect on VEGFR-2 in comparison to the Zdimer-4RepCT. The conclusion was drawn that Ztetramer coupled to 4RepCT with or without FN may impose an inducive effect upon VEGFR-2 although further studies need to be conducted.

  • 20.
    Alimjanova, Aziza
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Hur vanligt är det med terapimisslyckande med SSRI-preparat?2016Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
  • 21.
    Alkhazaali, Sarah
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Samband mellan nitrofurantoin och fosterskador vid behandling av urinvägsinfektion under graviditet2018Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [sv]

    Urinvägsinfektion (UVI) är bland de vanligaste bakteriella infektionerna som drabbar alla delar av urinvägarna såsom njurar, urinledare, urinblåsan, och urinrör. Gravida kvinnor löper ökad risk att drabbas av urinvägsinfektion som kan leda till njurbäckeninflammation på grund av bland annat den hormonella omställningen.En annan faktor som kan öka risken för urinvägsinfektion är tillståndet glykosuri som drabbar ungefär 70 % av alla gravida kvinnor. Vid urinvägsinfektion ska behandlingen vara effektiv men det är även viktigt att iaktta försiktighet då fostret inte ska utsättas för risker. Därför bör valet av antibiotikum vara lämpligt och säkert för både mor och foster. Efter odling och resistensbestämning sätts behandling med antibiotika in enligt provsvaren. Vid behandling av akut cystit och asymtomatisk bakteriuri väljs i första hand nitrofurantoin eller pivmecillinam och en cefalosporin i andra hand.

    Syfte

    Syftet med denna litteraturstudie var att undersöka ett eventuellt samband mellan antibiotikaanvändning i första trimestern av graviditet och förekomst av fosterskador vid behandling av urinvägsinfektion med nitrofurantoin.

    Metod

    Detta examensarbete genomfördes som en litteraturstudie och är baserat på 5 vetenskapliga artiklar.

    Resultat

    Det observerades ingen statistiskt signifikant ökad risk för stora medfödda missbildningar vid exponering för nitrofurantoin under den första trimestern av graviditeten enligt data från kohortstudier. Dock kunde man i fall-kontrollstudier iaktta en statistiskt signifikant ökad risk för utveckling av bland annat läpp/gomspalt och hjärtmissbildningar hos foster, bland mödrar som tog nitrofurantoin. Ökad risk för läpp/gomspalt fanns även vid jämförelser med kontroller vars UVI behandlats med penicillin.

    Slutsats

    Ökad risk för fosterskador efter användning av nitrofurantoin under första trimestern av graviditet har inte med säkerhet kunnat fastläggas även om viss ökad risk har noterats i vissa studier. Detta handlar då om viss ökad risk för händelser som i sig är ganska sällsynta. Det kan dock vara rimligt att i första hand använda penicillin vid behandling av UVI hos gravida när detta är ett möjligt alternativ.

  • 22.
    Al-Masaraa, Nahil
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Terpenmetabolism i Artemisia annua: rekombinant produktion och karaktärisering av seskviterpensyntaser.2015Independent thesis Basic level (degree of Bachelor), 180 HE creditsStudent thesis
    Abstract [sv]

    Malaria är en tropisk sjukdom som orsakas av encelliga organismer, protozoer från Plasmodium släktet. Varje år drabbas ungefär en halv miljard människor av malaria och cirka en miljon av dessa dör. Okomplicerad malaria är en mild form av malaria som enligt WHO rekommendationer ska behandlas med artemisinin baserad kombinationsterapi (ACT). Artemisinin produceras naturligt i låg mängd från växten Artemisia annua. Trots att medicinen har visat sig effektiv mot malaria med färre biverkningar är den höga kostnaden en nackdel. Forskning pågår för att hitta nya syntetiska vägar för framställning av artemisinin i växten genom att studera terpenmetabolism och vilka aktiva enzymer det finns som har en avgörande roll i utbytet av artemisinin i växten. Syftet med denna studie var att med hjälp av genteknik och molekylärbiologiska metoder producera och identifiera två rekombinanta enzymer, seskviterpensyntaser från A. annua. Experimentet inleddes med att transformera klonade T-DNA (AaTS-1 och AaTS-2) som kodar för seskviterpensyntaser från A. annua med hjälp av Agrobacterium tumefaciens vartefter transienta transkriptionen av generna som finns i en binär vektor initierades i blad från växten Nicotiana benthamiana genom infiltration. Totalt RNA extraherades från växten och översattes till cDNA för att sedan studera förhållandet av transient uttryck i bladen med qPCR. Enzymerna extraherades från bladen och inkuberades med farnesyldifosfat övernatt och produkten identifierades följande dag med gaskromatografi-masspektrofotometri (GC-MS). Resultatet blev att inget genuttryck av AaTS-1 och AaTS-2 kunde detekteras i bladen. Resultat från GC-MS visade att ingen proteinprodukt genererades. De negativa resultaten berodde främst på brist av resultat som verifierar att plasmiderna var konstruerade med selektionsgenerna, men även på grund av en icke effektiv transformation, orsakad av bakteriecellklumpar som förhindrade infiltreringsmedium att nå inre delarna av bladen.    

  • 23.
    Alnehmry, Shaima
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Effektiviteten av läkemedelsbehandling för att minska muntorrhet och förebygga karies2016Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    Background: Dry mouth (xerostomia) is a common symptom which is connected with hypofunction of salivary glands induced by transient physiological conditions, pathology or as a side effect of drugs or radiation. Xerostomia almost always develops after destruction of salivary glands in connection with the treatment of head and neck cancer with ionizing radiation. Certain autoimmune diseases such as Sjogren's syndrome can also give dry mouth symptoms. The use of anticholinergic drugs and certain antihistamines may also cause a decrease in salivation. Aging is another factor that can induce salivary gland hypofunction due to physiological changes and/or use of medications. The treatment goals for patients with dry mouth is to relieve symptoms, prevent or ameliorate the consequences of salivary dysfunction, and treating the underlying disease. Treatments to improve function include saliva stimulation and saliva substitutes with fluoride. The systemic drugs bromhexine and pilocarpine are tested as saliva stimulants. Pilocarpine (Salagen) is a non-selective muscarinic agonist that increases the secretion of saliva.

    The purpose of this thesis was to investigate the effect of drug treatments to reduce dry mouth and prevent tooth decay, with the help of scientific articles.

    Results showed that in patients with some remaining unstimulated salivary flow rate daily treatments with a fluoride concentration of 0.42% F was enough to prevent tooth decay to a large extent. Use of 1.23% F-gel was not better than the 0.42% gel treatment. Casein derivatives complexed with calcium phosphate could be an alternative to fluoride treatment. Salivary secretion increased significantly after mouth rinse with 1% or 2% pilocarpine with a plateau between 45 and 75 minutes. 2% pilocarpine solution also increased the sense of salivary flow. Dry mouth was improved in 12.1; 63.6; 69.7 % of the patients who received Salagen tablets (5mg pilocarpine hydrochloride), 3mg or 5mg pilocarpine lozenge, respectively, compared with 42.4 % of patients receiving placebo lozenge. Mouth wash with pilocarpine 0.1% increased secretion from minor salivary glands and whole unstimulated saliva secretion compared to 0.9% saline mouthwash. The effectiveness in relieving subjective dry mouth was not significantly different between the solutions.

    Conclusions: Patients with unstimulated salivary flow <0.1 ml / min have a higher risk of caries lesions compared to unstimulated salivary flow> 0.1 ml / min. Patients with stimulated salivary flow <0.5 ml / min have a higher risk of caries lesions compared to stimulated salivary flow >0.5 ml / min. Mouthwash with pilocarpine solutions at concentrations of 1-2% pilocarpine induce a significant objective and subjective dose dependent increase in salivary flow. Pilocarpine lozenge produced the better clinical responses and a faster subjective improvement of dry mouth than Salagen tablets.

  • 24.
    Alqaysi, Faeza
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Effekter av befintliga och eventuella framtida läkemedelsbehandlingar på morbiditet och mortalitet hos patienter med hjärtsvikt.2015Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    Background:  Heart failure is a multidimensional phenomenon with high mortality. Heart failure is treated with angiotensin converting enzyme (ACE) - inhibitors or angiotensin receptor blockers (ARBs) that counteract neurohormonal stimuli that occur in heart failure, as well as providing vessel dilatation, which reduces symptoms and the need for hospitalization and increases survival. Despite this, only about 50% of heart failure patients survive 6 years after diagnosis with drug therapy, and as heart failure is increasing globally, due to improved care and treatment and increasing life expectancy of the population, there is a great need for new drugs such as LCZ696 that acts by dual inhibition of the renin - angiotensin - aldosterone system and neprilysin inhibition.

    Objective: The aim of this literature study was to evaluate the efficacy of current treatment and possible future treatments on mortality and morbidity in heart failure patients.

    Results: The examined articles show that treatment with ACE inhibitors in patients with symptomatic heart failure reduces the risk of total mortality by 16% over 3.5 years, reduces all-cause mortality or hospitalization due to heart failure with NNT (number needed to treat) = 10.4 over 3.5 years and increases median survival by 9.2 months over 12.1 years in patients with asymptomatic heart failure. Treatments with high-dose ACE inhibitors reduce mortality and hospitalization because of cardiovascular causes and hospitalizations from any cause by NNT = 30 over 3 years. Beta-blockers reduce sudden death and total mortality and cardiac death or non - fatal myocardial infarction with NNT = 38 and NNT = 23, respectively, over 12 months. Treatment with the new drug LCZ696 reduces mortality due to cardiovascular causes with NNT = 21 over 27 months, reduces hospitalizations due to heart failure with NNT = 36 over 27 months and reduces deaths from any cause with NNT = 34 compared to treatment with ACE inhibitors.

    Conclusion: The studies show that both ACE inhibitors and beta-blockers have clear beneficial effects in the treatment of heart failure. Treatment with ACE inhibitors for 3.5 years compared to placebo reduces total mortality by a NNT value of about 22. Treatment with beta-blockers during 1 year compared with placebo reduces total mortality by a NNT value of 24. Treatment with the new drug LCZ 696 for 27 months compared with ACE inhibitors reduces total mortality with a NNT value of 36. One remaining problem is that 50% of patients with severe heart failure (NYHA class IV) die within a year.

  • 25.
    Al-Seadi, Sara
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Leva med ADHD: En intervjustudie2016Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
  • 26.
    Amann, Laura
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Development and Validation of an Analytical Method for Phenolic Acid Extraction from Cereals and Quantification using HPLC-UV2018Independent thesis Advanced level (degree of Master (Two Years)), 30 credits / 45 HE creditsStudent thesis
    Abstract [en]

    Cereals are rich in phenolic acids, a group of secondary plant metabolites that are associated with reduced risk of chronic diseases. The objective was to develop and internally validate a method for extraction and quantification of phenolic acids in cereals using HPLC-UV and to apply this method for quantification of the content of phenolic acids in several species of Swedish cereals. Different procedures for extraction of phenolic acids from cereal grains using acid or base hydrolysis with and without subsequent enzymatic treatment were tested. Both the extraction procedure and the chromatographic conditions for quantification with HPLC-UV were optimized. Phenolic acids from 14 cereal samples, representing different cultivars of rye, wheat, barley, and oat, were extracted and analyzed under optimized conditions. Using the optimized method, 15 phenolic acids could be quantified with limits of detection and quantification ranging from 0.4 to 11.4 µg/g and from 1.3 to 38.0 µg/g, respectively. The hydrolysis procedure and further sample treatment showed a substantial effect on the yield of phenolic acids from cereals. The highest yield was achieved by 90‑minute base hydrolysis at room temperature using sodium hydroxide solution containing ascorbic acid and EDTA. Mean recoveries ranged from 88 to 108%. The following phenolic acids were found in the analyzed cereal grains with ferulic acid being the most abundant one: p‑hydroxybenzoic acid, vanillic acid, vanillin, caffeic acid, syringic acid, ferulic acid, sinapic acid, and 3,4‑dihydroxybenzaldehyde. A further compound was p‑coumaric acid or the co‑eluting syringaldehyde or a mixture of both. The content of phenolic acids in Swedish cereals ranged from 6 µmol/g DM in rye to 3 µmol/g DM in oat and a barley cultivar. In conclusion, a simple and accurate method for extraction and quantification of phenolic acids in cereals was developed and successfully applied.

  • 27.
    Andersson, Carina
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Påverkar statiner effekter av fysisk aktivitet/skelettmusklernas funktion?2018Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [sv]

    Bakgrund: I Sverige år 2016 drabbades 25 700 personer av akut hjärtinfarkt och 25% av dem dog inom en månad. Ungefär 19% av Sveriges befolkning dvs 1,9 miljoner människor lever med en hjärtkärlsjukdom. År 2017 dog 31 616 svenskar av hjärtkärlsjukdom och det motsvarar 35,2% av alla avlidna svenskar det året. Dyslipidemi är en av de bakomliggande orsakerna till olika hjärtkärlsjukdomar och preparat vid behandling av dyslipidemi är i första hand statiner. Statiner är dessvärre kända för biverkningar såsom lever- och muskelpåverkan vilket har väckt frågan om de även påverkar effekter av fysisk aktivitet negativt. En eventuell interaktion mellan statiner och fysisk aktivitet skulle minska dess behandlande syfte då både statiner och fysisk aktivitet sägs sänka blodlipiderna. Syfte: Studiens syfte var att undersöka om statiner påverkar effekter av fysisk aktivitet/ skelettmusklernas funktion. Metod: Detta gjordes genom sökning efter relevanta artiklar på PubMed för att sedan sammanställa resultat från vetenskapliga artiklar inom området. Sökord som användes var ”statins physical activity”. Resultat: Det råder delade meningar gällande statiners ev. interaktion med effekter av fysisk aktivitet fast övervägande resultat pekar på att statiner inte påverkar effekter av fysisk aktivitet negativt. Även när det gäller muskelpåverkan som tex myalgi så är det svårt att koppla det till statinanvändningen. Däremot föreligger det inga delade meningar när det gäller statiners effekt som lipidsänkande läkemedel. Slutsats: Det är övervägande studieresultat som tyder på att statiner inte påverkar effekter av fysisk aktivitet/ skelettmuskelfunktion negativt men trots detta så fortsätter inrapportering av biverkningar som statininducerad muskelpåverkan att ske. Framtida forskning kanske kräver andra tillvägagångssätt, studiemarkörer etc. för att kunna påvisa ev. interaktioner mellan statiner och effekter av fysisk aktivitet/ skelettmuskelfunktion.

  • 28.
    Andersson, Fredrik
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Studies on organic liquid baby-food gruel: The effect of including organic flour and starch from corn2013Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    Introduction: Studies conducted on foods aimed for infants and young children have shown that foods containing rice have a high content of arsenic and cadmium. Arsenic and cadmium are toxic elements classified as carcinogens. It is therefore especially important to keep the levels low in foods for infants and young children since they have a high intestinal absorption and since the negative effects become apparent only after many years of chronic exposure.

    Aim: The aim of this project was to investigate if the rice flour in baby-food gruel could be replaced with corn flour with the aim to decrease the content of primarily arsenic and cadmium and sustain low levels of lead and mercury while retaining sensory properties. A native corn starch was also evaluated in terms of heavy metal content and sensory properties.

    Material & Methods: The rice flour in 4 different recipes was replaced with various proportions of flour and starch from corn whereon sensory evaluations were performed. Stability and viscosity measurements were conducted and the content of arsenic, cadmium, lead and mercury was analysed.

    Results/Conclusion: No differences in texture and mouth feel could be perceived at low corn flour concentrations when mixed with rice flour. Replacement of 60% of the rice flour fraction with corn flour in a gruel which contained 1.1% rice flour (w/w), may have led to an increased arsenic content. The corn starch provided the highest viscosity and had a smoother mouth feel at the same concentration compared to the corn flour and might be a better choice than the corn flour. In addition, corn starch had a lower content of cadmium and lead compared to the corn flour but further research is needed to establish which one contains the lowest level of arsenic. Both had a lower content of arsenic compared to the rice flour when the flours were analysed separately.

  • 29.
    Andersson, Håkan S.
    et al.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Jacobsson, Erik
    Uppsala University.
    Eriksson, Camilla
    Uppsala University.
    Hedström, Martin
    Lund University.
    Seth, Henrik
    Gothenburg University.
    McEvoy, Eric G
    Sundberg, Per
    Gothenburg University.
    Strand, Malin
    Swedish agricultural university (SLU).
    Discovery of peptide toxins in the world’s longest animal (The bootlace worm; Lineus longissimus): challenging claims of tetrodotoxin production.2015Conference paper (Other academic)
  • 30.
    Andersson, Håkan S.
    et al.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Jacobsson, Erik
    Uppsala University.
    Eriksson, Camilla
    Uppsala University.
    Hedström, Martin
    Lund University.
    Seth, Henrik
    University of Gothenburg.
    McEvoy, Eric G
    Liverpool John Moores University.
    Sundberg, Per
    University of Gothenburg.
    Strand, Malin
    Swedish University of Agricultural Sciences.
    Göransson, Ulf
    Uppsala University.
    Discovery of peptide toxins in ribbon worms: challenging claims of tetrodotoxin production2015Conference paper (Other academic)
  • 31.
    Andersson, Håkan S.
    et al.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Jacobsson, Erik
    Uppsala University.
    Eriksson, Camilla
    Uppsala University.
    Hedström, Martin
    Lund University.
    Seth, Henrik
    University of Gothenburg.
    Sundberg, Per
    University of Gothenburg.
    Rosengren, Johan
    University of Queensland.
    Strand, Malin
    Swedish University of Agricultural Sciences.
    Göransson, Ulf
    Uppsala University.
    The toxicity of ribbon worms: alpha-nemertides or tetrodotoxin, or both?2016In: Planta Medica, ISSN 0032-0943, E-ISSN 1439-0221, Vol. 82, no Supplement 1, article id P549Article in journal (Other academic)
    Abstract [en]

    The marine ribbon worms (nemerteans) are predators which capture their prey by everting a proboscis carrying a mixture of toxins which brings on rapid paralysis [1]. Moreover, ribbon worms have a thick layer of epidermal mucus of similar constitution. Tetrodotoxin (TTX) has been identified as one of these toxins [2]. The extreme toxicity of TTX (lethal by ingestion of 0.5-2 mg) is due to its ability to block voltage-gated sodium channels. Although several bacterial species (among these Vibrio sp.) have been linked to its synthesis, the biogenic origin and biosynthesis is unclear. One hypothesis is that TTX production occurs in a symbiotic relationship with its host, in this case the ribbon worm [3]. We have made significant effort to identify TTX in a setup for production through the cultivation of Vibrio alginolyticus in nutrient broth infused with mucus from the ribbon worm Lineus longissimus. Toxicity was demonstrated by fraction injections into shore crabs, but no TTX was found, and it could be shown conclusively that toxicity was unrelated to TTX and the Vibrio culture itself, and rather a constituent of the ribbon worm mucus [4]. The following studies led us to the discovery of a new class of peptides, the alpha-nemertides, in the mucus of the ribbon worms, which could be directly linked to the toxic effects. A literature review of the available evidence for TTX in ribbon worms show that the evidence in most cases are indirect, although notable exceptions exist. This points to the necessity to further investigate the presence and roles of TTX and alpha-nemertides in ribbon worms.

  • 32.
    Andersson, Håkan S.
    et al.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Jacobsson, Erik
    Uppsala University.
    Eriksson, Camilla
    Uppsala University.
    Rosengren, K. Johan
    University of Queensland, Australia.
    Andrén, Per
    Uppsala University.
    Strand, Malin
    Swedish agricultural university (SLU).
    Göransson, Ulf
    Uppsala University.
    Discovery of peptide toxins in the bootlace worm, the world's longest animal2015Conference paper (Other academic)
  • 33.
    Andersson, Håkan S
    et al.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Jacobsson, Erik
    Uppsala University.
    Laborde, Quentin
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Rosengren, Johan
    University of Queensland.
    Strand, Malin
    Swedish agricultural university (SLU).
    Göransson, Ulf
    Uppsala University.
    Alpha-nemertides - a novel family of nemertean peptide neurotoxins2018Conference paper (Other academic)
  • 34.
    Andersson, Håkan S.
    et al.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Jacobsson, Erik
    Uppsala University.
    Rosengren, Johan
    University of Queensland, Australia.
    Strand, Malin
    Swedish University of Agricultural Sciences.
    Göransson, Ulf
    Uppsala University.
    Discovery of novel ion-channel active peptide toxins in a North Sea Ribbon Worm2016Conference paper (Other academic)
    Abstract [en]

    Ribbon worms (nemerteans) are marine predators, which capture their prey using a proboscis containing a mixture of toxins which brings on rapid paralysis [1]. In addition, their epidermis contains thick mucus of similar toxic constitution. One very potent toxin reported in ribbon worm mucus is tetrodotoxin (TTX). However, despite significant efforts, Strand et al. [2] were unable to detect any TTX, neither in the mucus of the ribbon worm Lineus longissimus, nor from Vibrio alginolyticus cultures isolated from and cultivated in the mucus. These observations challenged the notion of general presence of TTX in ribbon worm mucus, and prompted us to look for other toxins [3]. Using LC-MS analysis of mucus extracts, we identified three peptides present in significant amounts. The peptides were sequenced using a combination of MS/MS analysis and transcriptomics, and whereas one of them strongly resembles the only peptide toxin previously characterized from ribbon worms, Neurotoxin B-IV [4], the other two were found to represent a previously unknown class of peptide toxins. The most abundant of these was synthesized, and its 3D structure determined. Preliminary toxicity tests on shore crab (C. maenas) indicated toxicity (through paralysis) on par with that of TTX. Further analyses have indicated that its toxic effects are due to binding to voltage sensitive sodium channels.

     

    With L. longissimus as our primary target, we are now mapping the presence of peptide toxins in ribbon worms, with the objectives to establish routes for synthesis, and to characterize the biological activities and structures of these peptides. The number of peptides of this novel class is increasing, and synthesis and characterization is well underway. The striking potencies of these peptides make them potentially amenable as novel insecticidal or anthelmintic leads, pharmacological tools or in biotechnology applications.

     

    References

    1. Strand M, Sundberg P. Nationalnyckeln till Sveriges flora och fauna [DO-DP]. Stjärnmaskar-Slemmaskar: Sipuncula-Nemertea: Artdatabanken, SLU; 2010.

    2. Strand M, Hedstrom M, Seth H, McEvoy EG, Jacobsson E, Goransson U, Andersson HS, Sundberg P. The Bacterial (Vibrio alginolyticus) Production of Tetrodotoxin in the Ribbon Worm Lineus longissimus-Just a False Positive? Marine Drugs. 2016;14(4).

    3. Strand M, Andersson HS. Slemmaskens hemlighet. Forskning & Framsteg. 2016;(2):26-33.

    4. Blumenthal KM, Kem WR. Structure and action of heteronemertine polypeptide toxins. Primary structure of Cerebratulus lacteus toxin B-IV. The Journal of Biological Chemistry. 1976;251(19):6025-9.

  • 35.
    Andersson, Håkan S
    et al.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Jacobsson, Erik
    Uppsala University.
    Rosengren, Johan
    University of Queensland.
    Strand, Malin
    Swedish agricultural university (SLU).
    Göransson, Ulf
    Uppsala University.
    Mapping the diversity of nemertean peptide toxins2018Conference paper (Other academic)
  • 36.
    Andersson, Håkan S.
    et al.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Jacobsson, Erik
    Uppsala University.
    Strand, Malin
    Swedish agricultural university (SLU).
    Peigneur, Steve
    University of Leuven (KU Leuven), Belgium.
    Lebbe, Eline
    University of Leuven (KU Leuven), Belgium.
    Rosengren, Johan
    University of Queensland.
    Tytgat, Jan
    University of Leuven (KU Leuven), Belgium.
    Göransson, Ulf
    Uppsala University.
    Alpha-nemertides, a novel family of marine peptide neurotoxins from ribbon worms2017Conference paper (Other academic)
  • 37.
    Andersson, Jeanette
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Finns det något värde i att mäta Peptide tyrosine tyrosine, Glucose-dependent insulinotropic polypeptide och Oxyntomodulin postprandialt vid måltidsstudier?2015Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [sv]

    Övervikt och fetma sprider sig likt en epidemi över världen. Omkring 1,9 miljarder vuxna varöverviktiga år 2014 och av dessa klassificerades 600 miljoner som feta. Forskning kring fetmas uppkomst och nya former av behandlingsalternativ pågår. En viktig faktor för uppkomst av övervikt är aptitreglering, där t.ex. Peptide tyrosine tyrosine (PYY), Oxyntomodulin (OXM) och Glucosedependent insulinotropic polypeptide (GIP) har betydelse. En litteraturstudie genomfördes där totalt nio originalartiklar från PubMed utvärderades. Syftet var att undersöka om det finns något värde i att mäta dessa hormon postprandialt. Finns det någon skillnad mellan normalviktiga, överviktiga och obesa och finns det någon skillnad mellan individer med typ 2-diabetes mellitus (T2DM) och friska individer? Finns det någon pålitlig analysmetod? Samtliga studier var måltidsstudier där olika näringsämnens påverkan på den postprandiala responsen undersöktes. Peptide tyrosine tyrosine ochGlucose-dependent insulinotropic polypeptide mättes i sex resp. fem av artiklarna och OXM mättes ien artikel. Protein, fett och kolhydrater ger en postprandial respons på PYY och GIP. Responsen av PYY var starkast efter stimuli från fett och protein. Fett tycks ge starkast respons på GIP. Fastevärden av PYY och GIP var inte olika hos normalviktiga och överviktiga i de studier som undersöktes. Det fanns en signifikant skillnad (p=0,01) mellan normalviktiga och överviktiga tonårsflickor av den postprandiala utsöndringen av PYY efter fettrik måltid, där de obesa flickorna hade lägre procentuell ändring jämfört med de normalviktiga. Pålitliga analysmetoder vid koncentrationsbestämning av dessa tre hormon i plasma är Radioimmunoassay (RIA) och Enzyme-linked immunosorbent assay (ELISA).

  • 38.
    Andersson, Louise
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Hur sker prioriteringar av resurser för att bekosta särläkemedel?: Cerezyme® – en fallstudie2013Independent thesis Basic level (professional degree), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    The choice of my thesis is based on orphan drugs, which individuals with rare diseases use as treatment, diagnostics or to prevent the progress of the disease. In order to get a classification as an orphan drug, the drug must be used for a condition that affects 5 or less of 10 000 individuals, based on the European classification. The clinical trials for this type of medicines are as every medical trial, expensive and orphan drugs have the smallest patient groups. Therefore there is no justification to the pharmaceutical companies in development in orphan drugs. This project is made by a case study and answer survey, and the literature research was based on articles written in English or Swedish, and articles older than 2000 were excluded.The purpose of this thesis is to evaluate how priorities of resources are made, to fund expensive drugs, in Sweden. Tandvårds- och läkemedelsförmånsverket (TLV) has the authority to decide whether different kind of medicines are subjects to the Swedish pharmaceutical benefits, which are funding a great amount of medicines. The thesis is based on evaluations from various stakeholder, Swedish laws and previous research in priority.Sweden is financing the orphan drugs in three ways. Orphan drugs included in Swedish pharmaceutical benefits are funded by customs fee to 2200 SEK, and the rest of the costs are financed by the state through the council counties. Orphan drugs in hospitalization are financed by the hospital, clinic or the county where the patient is registered. The orphan drugs which are prescribed but still excluded from the benefits are financed either by the patient, county or the hospital. The investigation of pricing and financial proposition of orphan drugs in Sweden is delayed but still in progress, and are expected to be presented in April, 2014.TLV make the decisions regarding pharmaceutical benefits through calculations of QALY’s and by three ethical grounds or principles. The principles stand for human dignity, cost-effectiveness, solidarity and needs. TLV could either approve the drug, which makes the drug included to pharmaceutical benefits, or disapprove the drug and makes it unavailable through state funding. TLV decided to exclude Cerezyme® from the Swedish pharmaceutical benefits. The decisions were made of calculations of QALY’s, which was calculated much higher costs than previously approved by TLV. The manufacturers of Cerezyme® did not agree with TLV’s decision, and went to higher courts. The recent decision of higher courts was to re-include Cerezyme® from pharmaceutical benefits, which makes the drug available to patients in desperate need again.Processes of different kinds of orphan drugs to include these to pharmaceutical benefits are not treated equally. Depending of the state of the disease, prevalence and geographic location, are patients treated variously. This is a major problem in management of orphan drugs, and should be prevented as soon as possible. All citizens should on equal terms, have access to same health care, this through Swedish Health Care laws.

  • 39.
    Andre, Ingemar
    et al.
    Lund University.
    Bjelic, Sinisa
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Computational assessment of folding energy landscapes in heterodimeric coiled coils2018In: Proteins: Structure, Function, and Bioinformatics, ISSN 0887-3585, E-ISSN 1097-0134, Vol. 86, no 7, p. 790-801Article in journal (Refereed)
    Abstract [en]

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

  • 40.
    Angeland, Malin
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Inverkan av n-3-fettsyror vid förlossningsdepression.2015Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [sv]

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

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

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

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

  • 41.
    Angviken, Åsa
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    SSRIs effekt och säkerhet hos barn och ungdomar2016Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [sv]

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

  • 42.
    Apostolou, Vasileios
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Identification of covalently labeled, non-catalytic residues in proteins using liquid chromatography–mass spectrometry techniques2018Independent thesis Advanced level (degree of Master (One Year)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

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

  • 43.
    Areda, Martha
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    The role of omega-3 fatty acids in the treatment of schizophrenia through modification of membrane phospholipids2016Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

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

  • 44.
    Arndt, Corinna
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Försäljning och förskrivning av antidepressiva läkemedel ur genusperspektiv.2017Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

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

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

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

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

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

  • 45.
    Asif, Sana
    et al.
    Uppsala University.
    Jonsson, Nina
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences. Uppsala University.
    Teramura, Yuji
    Univ Tokyo, Japan.
    Gustafson, Elisabet
    Univ Uppsala Hosp.
    Nilsson Ekdahl, Kristina
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences. Uppsala University.
    Nilsson, Bo
    Uppsala University.
    Conjugation of human recombinant CD39 to primary human hepatocytes protects against thromboinflammation2015In: Xenotransplantation, ISSN 0908-665X, E-ISSN 1399-3089, Vol. 22, p. S87-S87Article in journal (Other academic)
  • 46.
    Asif, Sana
    et al.
    Uppsala University.
    Nilsson Ekdahl, Kristina
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences. Uppsala University.
    Fromell, Karin
    Uppsala University.
    Gustafson, Elisabet
    Uppsala University Hospital.
    Barbu, Andreea
    Uppsala University.
    Le Blanc, Katarina
    Karolinska Institutet;Karolinska University Hospital.
    Nilsson, Bo
    Uppsala University.
    Teramura, Yuji
    Uppsala University;The University of Tokyo, Japan.
    Heparinization of cell surfaces with short peptide-conjugated PEG-lipid regulates thromboinflammation in transplantation of human MSCs and hepatocytes2016In: Acta Biomaterialia, ISSN 1742-7061, E-ISSN 1878-7568, Vol. 35, p. 194-205Article in journal (Refereed)
    Abstract [en]

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

  • 47.
    Ataei, Shakila
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Optimering av analysmetoden hos koldioxid-isotop-analysatorn, Picarro-G2131-i2015Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

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

     

    Conclusion

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

  • 48.
    Ataei, Tahereh
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Förekomst av penicillinkänslighet hos blododlingsisolat av Staphylococcus aureus2014Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

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

  • 49. Aveyard,, J
    et al.
    Hajne, J.
    Månsson, Alf
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Persson, Malin
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    van Delft,, F.C.M.J.M.
    van Zijl, J.
    Snijder, J.
    van den Heuvel,, F.C.
    Nicolau,, D.V.
    Actin motility confinement on micro/nanostructured surfaces.2013In: Proc. SPI 8587, Imaging, Manipulation, and Analysis of Biomolecules, Cells, and Tissues XI, 858722 (February 22, 2013) / [ed] Daniel L. Farkas; Dan V. Nicolau; Robert C. Leif, SPIE - International Society for Optical Engineering, 2013, p. 858722-858727Conference paper (Refereed)
  • 50.
    Baftijaj, Jehon
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Etniska skillnader i läkemedelsrespons för substanser relevanta vid hjärt-kärlsjukdomar2017Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

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

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

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

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

     

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

     

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

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