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  • 301.
    Han, Junli
    et al.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Wang, Hongzhen
    Zhejiang Agr & Forestry Univ, Peoples Republic of China.
    Kanagarajan, Selvaraju
    Swedish University of Agricultural Sciences.
    Hao, Mengshu
    Lund University.
    Lundgren, Anneli
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Brodelius, Peter E.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Promoting Artemisinin Biosynthesis in Artemisia annua Plants by Substrate Channeling2016In: Molecular Plant, ISSN 1674-2052, E-ISSN 1752-9867, Vol. 9, no 6, p. 946-948Article in journal (Refereed)
  • 302.
    Han, Junli
    et al.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Wang, Hongzhen
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences. Zhejiang Agriculture and Forestry University, Linan 311300, Zhejiang, PR China..
    Lundgren, Anneli
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Brodelius, Peter E.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Effects of overexpression of AaWRKY1 on artemisinin biosynthesis in transgenic Artemisia annua plants2014In: Phytochemistry, ISSN 0031-9422, E-ISSN 1873-3700, Vol. 102, p. 89-96Article in journal (Refereed)
    Abstract [en]

    The effective anti-malarial medicine artemisinin is costly because of the low content in Artemisia annua. Genetic engineering of A. annua is one of the most promising approaches to improve the yield of artemisinin. In this work, the transcription factor AaWRKY1, which is thought to be involved in the regulation of artemisinin biosynthesis, was cloned from A. annua var. Chongqing and overexpressed using the CaMV35S promoter or the trichome-specific CYP71AV1 promoter in stably transformed A. annua plants. The transcript level of AaWRKY1 was increased more than one hundred times under the CaMV35S promoter and about 40 times under the CYP71AV1 promoter. The overexpressed AaWRKY1 activated the transcription of CYP71AV1 and moreover the trichome-specific overexpression of AaWRKY1 improved the transcription of CYP71AV1 much more effectively than the constitutive overexpression of AaWRKY1, i.e. up to 33 times as compared to the wild-type plant. However the transcription levels of FDS, ADS, and DBR2 did not change significantly in transgenic plants. The significantly up-regulated CYP71AV1 promoted artemisinin biosynthesis, i.e. up to about 1.8 times as compared to the wild-type plant. It is demonstrated that trichome-specific overexpression of AaWRKY1 can significantly activate the transcription of CYP71AV1 and the up-regulated CYP71AV1 promotes artemisinin biosynthesis.

  • 303. Hancock, Viktoria
    et al.
    Huang, Shan
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Nilsson, Anders
    Grundstrom, Gunilla
    Nilsson Ekdahl, Kristina
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Citrate reduces complement and leukocyte activation in vitro in human blood2013In: Nephrology, Dialysis and Transplantation, ISSN 0931-0509, E-ISSN 1460-2385, Vol. 28, p. 207-208Article in journal (Other academic)
  • 304.
    Hanna, Ilona
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Påverkar influensavirusinfektion det medfödda humorala immunförsvaret hos gräsänder?2018Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
  • 305.
    Hannasson, Amalia
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Prevalensen av Meticillinresistent Staphylococcus aureus CC/ST398 i länder som Sverige importerar mest kött ifrån och risk för spridning till Sverige.2019Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    Background: MRSA or Methicillin-resistant Staphylococcus aureus consists of several strains in the bacterial species called Staphylococcus aureus. MRSA is resistant to methicillin but also to other types of antibiotics. Spread can occur both directly between humans and between humans and animals, but also indirectly through air.

    The number of positive bacterial cultures for MRSA in Sweden increases every year. The prevalence of MRSA of different types varies in different countries. LA-MRSA is a livestock-associated methicillin-resistant Staphylococcus aureus that was first discovered in the Netherlands in pigs. This bacterial type belongs to a specific clone called CC398 (clonal complex 398), were most belonged to a specific sequence type called ST398 (multi locus sequence type 398). The CC398 strain are constantly acquiring new features including virulence factors such as the PVL-gene has been reported and associated with serious infections in humans and animals. This specific bacterial clone is found primarily in food producing animals around Europe, and it can infect humans and cause infection. It occurs mainly in pigs and can be spread through contaminated pork or other meat products to humans.

    Purpose: This work was aimed to survey the prevalence of LA-MRSA in the countries from which Sweden imports most meat from and to review the spread from meat products.

    Method: This study is been based on information on antibiotic use among food producing animals and the proportion of reported cases of MRSA in the countries from which meat was imported. Scientific studies in all countries was used to obtain information on the prevalence of MRSA CC/ST 398 and on its characteristics.

    Results: The countries from which Sweden imports most meat are Germany, Denmark and the Netherlands, pork import dominates. In 2018 there were 27,260 tonnes of pork imported from Denmark and 45,197 tonnes from Germany, compared with imports from the Netherlands, which amounted to 6,888 tonnes. Germany has the highest antibiotic consumption and the highest proportion of reported cases of MRSA among these countries.

    In Denmark, the CC/ST 398-clone caused 17 blood infections and 700 skin and soft tissue infections between 2010 and 2015. In Germany, 166 of 330 pigs examined in 2012 were positive for the same clone, as was 77 of the 134 collected samples from the environment and 39 of the 63 animal caretakers. In Brazil, CC / ST398 was found in 6 of 1852 children, genotypic characterization indicated it was an MSSA (methicillin-sensitive S. aureus) CC398 that had acquired SCCmec genes in the health care system. In Italy 81 of 215 pig isolates collected were positive for MRSA where the dominant type was CC / ST398. Virulence genes associated with human MRSA strains such as enterotoxin and PVL genes were not present among the pig isolates. Resistance to tetracycline was seen in all pig isolates. In the Netherlands, MRSA CC / ST398 was linked to pigs in that sense that the humans that were infected were exposed to pigs on a daily basis.

    Conclusion: The prevalence of LA-MRSA CC / ST398 was high in all the countries surveyed. Resistance to tetracyclines was significantly higher among pig isolates compared to HA-MRSA isolates (healthcare-associated MRSA), whereas the virulence genes such as the PVL- gene usually not present detected in pig- isolates. Among strains identified as LA-MRSA CC / ST398 acquired SCCmec-genes were of types V and IV.  The spread from pigs or meat was through direct contact but also through air.

  • 306.
    Harboe, Morten
    et al.
    Oslo University Hospital, Norway.
    Johnson, Christina
    Oslo University Hospital, Norway.
    Nymo, Stig
    Nordland Hospital, Norway.
    Ekholt, Karin
    Oslo University Hospital, Norway.
    Schjalm, Camilla
    Oslo University Hospital, Norway.
    Lindstad, Julie K.
    Oslo University Hospital, Norway.
    Pharo, Anne
    Oslo University Hospital, Norway.
    Hellerud, Bernt Christian
    Oslo University Hospital, Norway.
    Nilsson Ekdahl, Kristina
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences. Uppsala University.
    Mollnes, Tom Eirik
    Oslo University Hospital, Norway ; Nordland Hospital, Norway ; University of Oslo, Norway ; University of Tromsø, Norway ; Norwegian University of Science and Technology, Norway.
    Nilsson, Per H.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences. Oslo University Hospital, Norway ; University of Oslo, Norway.
    Properdin binding to complement activating surfaces depends on initial C3b deposition2017In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 114, no 4, p. E534-E539Article in journal (Refereed)
    Abstract [en]

    Two functions have been assigned to properdin; stabilization of the alternative convertase, C3bBb, is well accepted, whereas the role of properdin as pattern recognition molecule is controversial. The presence of nonphysiological aggregates in purified properdin preparations and experimental models that do not allow discrimination between the initial binding of properdin and binding secondary to C3b deposition is a critical factor contributing to this controversy. In previous work, by inhibiting C3, we showed that properdin binding to zymosan and Escherichia coli is not a primary event, but rather is solely dependent on initial C3 deposition. In the present study, we found that properdin in human serum bound dose-dependently to solid-phase myeloperoxidase. This binding was dependent on C3 activation, as demonstrated by the lack of binding in human serum with the C3-inhibitor compstatin Cp40, in C3-depleted human serum, or when purified properdin is applied in buffer. Similarly, binding of properdin to the surface of human umbilical vein endothelial cells or Neisseria meningitidis after incubation with human serum was completely C3-dependent, as detected by flow cytometry. Properdin, which lacks the structural homology shared by other complement pattern recognition molecules and has its major function in stabilizing the C3bBb convertase, was found to bind both exogenous and endogenous molecular patterns in a completely C3-dependent manner. We therefore challenge the view of properdin as a pattern recognition molecule, and argue that the experimental conditions used to test this hypothesis should be carefully considered, with emphasis on controlling initial C3 activation under physiological conditions.

  • 307.
    Harnebjer, Victoria
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Detektion av ESBL-CARBA med MALDI TOF-MS2015Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [sv]

    Under de senaste tio åren har man globalt sett en snabb spridning av karbapenemas (ESBL-CARBA)-producerande bakterier, bakterier som har förmågan att bryta ner alla betalaktamantibiotika inklusive karbapenemer. Detta är synnerligen allvarligt eftersom bakteriestammar med karbapenemas-produktion dessutom ofta har andra resistensfaktorer vilket kan innebära att de inte är behandlingsbara överhuvudtaget. Med en ökad prevalens behövs en snabb och tillförlitlig metod för detektion av karbapenemas-producerande stammar för att begränsa spridningen samt för att få lämplig information om initial behandling av infektioner orsakade av ESBL-CARBA. Syftet med det här arbetet var att sätta upp och utvärdera en kliniskt användbar metod för konfirmering av misstänkt karbapenemas-producerande bakterier vid det kliniska laboratoriet på Länssjukhuset i Kalmar. I första hand gjordes försök att detektera karbapenemasproduktion genom att efter inkubation av bakteriestam tillsammans med ertapenem analysera nedbrytningsprodukter av ertapenem med MALDI-TOF MS enligt Vogne et al. 2014. Trots att ertapenem-toppar kunde detekteras och upprepade försök med både provokation med ertapenem vid uppodling av stammar samt längre inkubationstid så gick det inte att erhålla en märkbar skillnad mellan resistenta och känsliga stammar samtidigt som repeterbarheten var låg. För jämförelse utfördes även en diffusionsmetod för karakterisering av karbapenemasaktivitet med typ-specifika karbapenemas-hämmare i tablettform. Diffusionsmetoden uppvisade både repeterbarhet och riktighet då uppmätta resultat stämde överens med redan genetiskt bekräftade karbapenemastyper.

  • 308.
    Harper, Aimee R.
    et al.
    New Zealand Inst Plant & Food Res Ltd, New Zealand.
    Unelius, C. Rikard
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences. New Zealand Inst Plant & Food Res Ltd, New Zealand.
    Townsend, Richard J.
    AgResearch Ltd, Lincoln Res Ctr, New Zealand.
    Suckling, David Maxwell
    New Zealand Inst Plant & Food Res Ltd, New Zealand.
    Dose reduction and alternatives to the phenol pheromone in monitoring and management of the grass grub Costelytra zealandica2017In: Pest Management Science, ISSN 1526-498X, E-ISSN 1526-4998, Vol. 73, no 11, p. 2252-2258Article in journal (Refereed)
    Abstract [en]

    BACKGROUNDEndemic New Zealand grass grub Costelytra zealandica is a pest of introduced pasture that uses phenol as a sex pheromone. The pheromone could be used to monitor and manage grass grub populations, but the irritating properties and toxicity of phenol for human handlers, as well as the possible ecotoxicological effects, pose obstacles to the deployment of the pheromone. This study aimed to limit the use of phenol by dose-response studies and investigation into alternative attractants and synergists to phenol. RESULTSNo difference in trap catch was seen across the range of 1-100mg of phenol, while rates below this (0.001-0.1mg) caused a large drop in catches. Our results indicated that 1mg loading in lures was enough to indicate beetle presence over 1 week. 4-Hydroxybenzaldehyde and p-cresol proved unattractive in this study, both as single attractants and as synergists with phenol. Phenyl acetate, phenyl benzoate and diphenyl carbonate all formed phenol under hydrolytic conditions to act as successful propheromones, while phenyl acetate was found to be as attractive as phenol on its own. CONCLUSIONThis study described several ways to reduce or avoid the use of phenol in the field while maintaining lure effectiveness. (c) 2017 Society of Chemical Industry

  • 309.
    Harrysson, Louise
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Kalibreringav mikrovågsinstrumentet HK1-Mc för ostarna Herrgård 17 % och Grevé 17 %2013Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    The present study investigated the water content and the height of the hard cheese varieties Herrgård with a fat content of 17% (H17%) and Grevé with a fat content of 17% (G17%). The aim of this study was to calibrate the microwave instrument HK1-Mc. The microwave instrument HK1-Mc uses the microwaves in combination with the product height and dielectric properties of water, to measure the water content in cheeses. The work began with a one-point calibration of the instrument, where obtained data were compared with assay values from an FTIR instrument, which was used as the reference method of analysis. The obtained measurement data from the microwave instrument and IR instrument where inserted into a spreadsheet program recommended by the manufacturer HK1-Mc, (Harrer & Kassen), from which the appropriate "slope" and "intercept" values were obtained for the microwave instrument. According to the measurements obtained on water from HK1-Mc respective FTIR instrument there is a correlation between the instruments of 1.1%.According to the measurements obtained from the instrument HK1-Mc, there is a correlation between water content and height of the cheeses, coefficient of determination of 60.4%, after calibration, this results can not be considered reasonable in the calibration of the instrument. According to measurements obtained from the reference instrument the relationship is significantly weaker, determintationskoefficient of 3.5% between water content and height after calibration, this value can be considered reasonable in the calibration of the instrument. The correlation between water content and height can be due to a change in the relationship between bound and free water because the height of the cheeses changes with time. The correlation may also be due to that the samples during calibration had a narrow distribution, which may have led to the “slope” of the calibration curve being incorrect. In the final stage of the work it was discovered that all of the previously calibrated channels in the microwave instrument provide a correlation between water content and height. The trend among all channels makes the current calibration unusable. There is a suspicion that the memory or height sensor of the instrument has been changed or influenced. Several other technical reasons can be the basis for the instrument's behavior. The cause / causes of the technical problems are under investigation.

  • 310.
    Hashim Bashir, Nazdar
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Rifaximin som behandling vid Small Intestinal Bacteria Overgrowth (SIBO)2019Independent thesis Basic level (degree of Bachelor), 10 HE creditsStudent thesis
    Abstract [en]

    SIBO (Small Intestinal Bacterial Overgrowth) is a condition where the small intestine is colonized by bacteria normally found in the large intestine. SIBO develops when the normal homeostatic mechanisms controlling the enteric bacterial population are disrupted. In the small intestine, there should be very small number of bacteria while in the large intestine there should be much larger number of bacteria. When the bacteria colonizes the small intestine, it results in SIBO. This bacterial imbalance in the small intestine can cause bloating, diarrhea and stomach pain, constipation and impaired absorption of vitamins and nutrients. Treating the underlying cause of SIBO is the first step in the treatment and if this is not enough, antibiotic treatment is the next step.

    The purpose of this literature study was to investigate the effectiveness of Rifaximin in treatment of bacterial overgrowth in the small intestine (SIBO). The study is a literature study where the scientific articles were obtained from the database Pubmed. In this literature study, five studies have been analyzed. Study I showed that high-dose treatment with rifaximin significantly increased treatment efficacy compared to low-dose treatment. Study II showed that a combination of amoxicillin and rifaximin can be an effective first-line treatment for patients who have both SIBO and H. pylori infection. Study III confirmed that SIBO is underdiagnosed in CF patients, related to poor nutritional status. Rifaximin is an effective treatment for SIBO in patients who have CF. Study IV also showed a combination treatment where rifaximin together with hydrolyzed guar gum appears to be more effective in eradicating SIBO compared to rifaximin alone. Study V studied rifaximin-treated IBS patients, rifaximin treatment was associated with acceleration of colon transit, and a weak influence on changes in microbial species richness in faeces. Based on the five studies, there is reasonable evidence that a treatment with rifaximin is an effective treatment for SIBO. However, more research and studies are needed to determine the best dose and also rifaximin in combination with other drugs.

  • 311.
    Haugaard-Kedström, Linda M.
    et al.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences. Univ Queensland, Australia.
    Hossain, Mohammed Akhter
    Univ Melbourne, Australia.
    Daly, Norelle L
    Univ Queensland, Australia.
    Bathgate, Ross A D
    Univ Melbourne, Australia.
    Rinderknecht, Ernst
    Novartis Corp, USA.
    Wade, John D
    Univ Melbourne, Australia.
    Craik, David J
    Univ Queensland, Australia.
    Rosengren, K. Johan
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences. Univ Queensland, Australia.
    Solution Structure, Aggregation Behavior, and Flexibility of Human Relaxin-2.2015In: ACS Chemical Biology, ISSN 1554-8929, E-ISSN 1554-8937, Vol. 10, no 3, p. 891-900Article in journal (Refereed)
    Abstract [en]

    Relaxin is a member of the relaxin/insulin peptide hormone superfamily and is characterized by a two-chain structure constrained by three disulfide bonds. Relaxin is a pleiotropic hormone and involved in a number of physiological and pathogenic processes, including collagen and cardiovascular regulation and tissue remodelling during pregnancy and cancer. Crystallographic and ultracentrifugation experiments have revealed that the human form of relaxin, H2 relaxin, self-associates into dimers, but the significance of this is poorly understood. Here, we present the NMR structure of a monomeric, amidated form of H2 relaxin and compare its features and behavior in solution to those of native H2 relaxin. The overall structure of H2 relaxin is retained in the monomeric form. H2 relaxin amide is fully active at the relaxin receptor RXFP1 and thus dimerization is not required for biological activity. Analysis of NMR chemical shifts and relaxation parameters identified internal motion in H2 relaxin at the pico-nanosecond and milli-microsecond time scales, which is commonly seen in other relaxin and insulin peptides and might be related to function.

  • 312.
    Haurami, Hamiar
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    En optimering och utvärdering utav specialfärgningen Luxol-Fast-Blue2019Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [sv]

    Hjärt-kärlsjukdomar är de vanligaste dödsorsakerna i Sverige och under 2016 stod de för 35 % av alla dödsfall i Sverige. Vid behandling av hjärtinfarkt är målet att återställa blodflödet till hjärtat. Trots att återställandet av blodflödet (reperfusion) till hjärtat leder till förbättrat kort- och långsiktigt hälsotillstånd så kan reperfusionen leda till irreversibla skador såsom kardiell kontraktionsbandsnekros. Luxol-fast-blue är en specialfärgning som används för att undersöka myelin samt visats färga in myofibrilla degenereringar såsom kontraktionsbandsnekros. Syftet med detta examensarbete var att göra det möjligt att påvisa akut hjärtinfarkt med luxor-fast-blue, en mer specifik färgmetod istället för rutindiagnostisk klassisk hematoxylin och eosin-färgning. Arbetet utfördes genom att vävnad från hjärta med känd hjärtinfarkt förbereddes och färgades med luxor-fast-blue. Metoden för infärgning med luxor-fast-blue modifierades för att uppnå optimal infärgning av kontraktionsbandsnekros vid hjärtinfarkt. De olika modifikationerna som gjordes var ändrad tid vid infärgning, differentiering och kärninfärgning. Resultatet av arbetet visade att vävnaden, med hjärtinfarkt, som färgades med luxor-fast-blue över natt, differentieringen under 50 sekunder och kärninfärgning med nuclear-fast-red under en minut var den mest optimala infärgningen av kontraktionsbandsnekros vid hjärtinfarkt. Där kunde blå infärgade kontraktionsband visualiseras i hjärtinfarktsbiopsin medan resterande celler var infärgade rött.

  • 313.
    Hedman, Ellinore
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Probiotika som prevention mot urogenitala sjukdomar2014Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    About 10 % of the adult women population in Sweden are treated annually for urinary tract infections. The increasing bacterial resistance towards antibiotics is classified by WHO (World Health Organization) and ECDC (European Centre for Disease Prevention and Control) as one of the greatest treats for human health in a global perspective. To find alternatives scientists are studying the possibility to use probiotics to reduce the frequency of recurring urinary tract infections. This literature study examines five randomized double blinded placebo controlled studies where different strains of Lactobacillus have been used as a prophylactic to women suffering from recurrent urinary tract infections and bacterial vaginosis. Overall the studies do not display enough promising results to recommend the use of probiotics as a prophylax or cure.

  • 314.
    Hefni, Mohammed E.
    et al.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences. Mansoura Univ, Egypt.
    Amann, Laura S.
    Tech Univ Munich, Germany.
    Witthöft, Cornelia M.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    A HPLC-UV Method for the Quantification of Phenolic Acids in Cereals2019In: Food Analytical Methods, ISSN 1936-9751, E-ISSN 1936-976X, Vol. 12, no 12, p. 2802-2812Article in journal (Refereed)
    Abstract [en]

    Cereals are a good source of phenolic acids, most of which are present in bound form. The aim of this study was to develop a method for quantifying total phenolic acids in cereals that includes a robust step for hydrolysis of bound forms. Different hydrolysis procedures were evaluated. Acid hydrolysis, even with subsequent use of enzymes, proved unsuitable for releasing bound phenolic acids from the cereal matrix. Base hydrolysis (3 M, 90 min) resulted in the highest extractability, with average recoveries of 88-108% for cereal phenolic acids. The phenolic acid content in cereals (two cultivars each of rye, barley, and oats, and eight cultivars of wheat) varied up to 2-fold between cereal genotypes and 1.5-fold within genotypes. The highest content was found in rye, followed by wheat, barley, and oats. Ferulic acid dominated in all cereals, amounting to 48-72% of total phenolic acid content.

  • 315.
    Hefni, Mohammed E.
    et al.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences. Mansoura University, Egypt.
    Schaller, Franziska
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Witthöft, Cornelia M.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Betaine, choline and folate content in different cereal genotypes2018In: Journal of Cereal Science, ISSN 0733-5210, E-ISSN 1095-9963, Vol. 80, p. 72-79Article in journal (Refereed)
    Abstract [en]

    The importance of dietary methyl donors, e.g. betaine, choline and folate, is increasingly being recognised. This study examined variations in methyl donor concentrations in different cereals grown in Sweden. Fourteen cereal samples, representing different genera and cultivars, were analysed using HPLC- UV/FLD. The content of methyl donors in the cereals varied significantly due to cereal genotype. Betaine content varied most, with 28 mg/100 g DM in oats and 176 mg/100 g DM in rye. Total choline varied less, with 67 mg/100 g DM in rye and 149 mg/100 g DM in naked barley. In wheat, the lowest concentration of folate with 36 mg/100 g DM was found, and the highest of 91 mg/100 g DM in barley. Esterified choline was the major contributor to total choline content (80e95%) in the cereals. Free choline was less abundant, ranging from 3 to 27mg/100g DM. 5-CHO-H4folate was the dominant folate form in all cereals, amounting to approx. 35e50% of the sum of folates, as determined after pre-column conversion. Due to the limited number of available cultivars, no interpretation regarding effects from cultivar can be made. In conclusion, the studied cereal genotypes are good sources of methyl donors, but concentrations show considerable variation between different cereals.

  • 316.
    Hefni, Mohammed E.
    et al.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences. Mansoura University, Egypt.
    Shalaby, Mohamed T.
    Mansoura University, Egypt.
    Mohamed, Rasha A.
    Mansoura University, Egypt.
    Elwa, Ahmad M.
    Mansoura University, Egypt.
    Witthöft, Cornelia M.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Effect of a 12-Week Dietary Intervention with Folic Acid or Folate-Enhanced Foods on Folate Status in Healthy Egyptian Women2016In: Food and Nutrition Sciences, ISSN 2157-944X, E-ISSN 2157-9458, Vol. 7, p. 1339-1351Article in journal (Refereed)
    Abstract [en]

    The Egyptian government introduced wheat-flour fortification with iron and folic acid to reduce the incidence of neural tube defects, but suspended it for technical reasons. We previously developed novel legume foods with enhanced folate content. In this study, we investigated the efficacy of 12-week intervention with folate-en- hanced foods versus folic acid supplement in improving folate status in Egyptian women. A randomized, parallel intervention trial with two active groups (n = 19, n = 18) and one blinded control group (n = 20) was executed over 12 weeks. Volunteers received either germinated legume foods and orange juice (≈250 μg/d folate) or folic acid supplement (500 μg/d) or apple juice (0 μg/d folate). Folate status was assessed by erythrocyte and plasma folate and total homocysteine (tHcy) at day 0, and after 8 and 12 weeks of intervention. After 12 weeks, mean plasma folate increased by 14 (P < 0.0001) and 12 (P < 0.0001) nmoL in the folic acid and food group, respectively. Erythrocyte folate concentration increased in the folic acid group from 614 to 912 (P < 0.0001) and in the food group from 631 to 914 nmoL (P < 0.0001). After 12 weeks, 90% of subjects in the folic acid group and 70% in the food group had erythrocyte folate concentrations exceeding 906 nmol/L. tHcy concentration was decreased by 20% (P = 0.007) and 18% (P = 0.006) in the folic acid and food group, respectively, but remained unchanged in the control group during intervention. Folate-enhanced foods effectively improve folate status in women of reproductive age. These foods could be used as a complement to folic acid fortification 

  • 317.
    Hefni, Mohammed E.
    et al.
    Mansoura University, Egypt.
    Witthöft, Cornelia M.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Egyptian Legumes and Cereal Foods: Traditional and New Methods for Processing2016In: Mediterranean Foods: Composition and Processing / [ed] Rui M. S. Cruz, Margarida C. Vieira, Boca Raton, FL: CRC Press, 2016, p. 102-120Chapter in book (Refereed)
    Abstract [en]

    Legumes and cereals play an important role in the traditional diet in several regions of the world (Messina 1999). In egypt, cereals occupy the first place in the human diet as a source of calories, with proteins and legumes as the second (FaO 2011). public health authorities around the world recommend the consumption of cereals and legumes because of health benefits deriving from their chemical composition, e.g., a low content of saturated fat and a high content of essential nutrients and phytochemicals (anderson 2004, Messina 2014).

  • 318.
    Hefni, Mohammed E.
    et al.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences. Mansoura Univ, Egypt.
    Witthöft, Cornelia M.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Moazzami, Ali
    Swedish University of Agricultural Sciences.
    Plasma metabolite profiles in healthy women differ after intervention with supplemental folic acid v. folate-rich foods2018In: Journal of Nutritional Science, ISSN 2048-6790, E-ISSN 2048-6790, Vol. 7, p. 1-9, article id e32Article in journal (Refereed)
    Abstract [en]

    Public health authorities recommend all fertile women to increase their folate intake to 400 μg/d by eating folate-rich foods or by taking a folic acid supplement to protect against neural tube defects. In a previous study it was shown that folate-rich foods improved folate blood status as effectively as folic acid supplementation. The aim of the present study was to investigate, using NMR metabolomics, the effects of an intervention with a synthetic folic acid supplement v. native food folate on the profile of plasma metabolites. Healthy women with normal folate status received, in parallel, 500 μg/d synthetic folic acid from a supplement (n 18), 250 μg/d folate from intervention foods (n 19), or no additional folate (0 μg/d) through a portion of apple juice (n 20). The metabolic profile of plasma was measured using 1H-NMR in fasted blood drawn at baseline and after 12 weeks of intervention. Metabolic differences between the groups at baseline and after intervention were assessed using a univariate statistical approach (P ≤ 0·001, Bonferroni-adjusted significance level). At baseline, the groups showed no significant differences in measured metabolite concentrations. After intervention, eight metabolites, of which six (glycine, choline, betaine, formate, histidine and threonine) are related to one-carbon metabolism, were identified as discriminative metabolites. The present study suggests that different folate forms (synthetic v. natural) may affect related one-carbon metabolites differently.

  • 319.
    Heirani, Pegah
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Hur effektiv och säker är en kombination av afoxolaner och milbemycinoxim mot gastrointestinala nematoder hos hund?2018Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    Research have shown positive effects of close relationships between humans and pets also known as the human-animal bond. Companion animals not only can influence socialization and mental abilities positively, but also improve physical well-being. Alongside of these advantages there are some zoonotic hazards which mustn't be underestimated. Drug treatment to reduce parasites has been used since anti parasitic substances were introduced in the mid-1900s. Now there are many different products, in different forms and in a variety of compounds. As studies haven’t shown any practical methods to minimize the level of eggs in the environment and prevent contamination, antiparasitic agents are our most important tool to control parasites and consequently to improve animal and public health.

    This thesis focuses on a quite new combination of an endo- and ectoparasite agent. NexGard Spectra®  contains the anthelmintic agent milbemycin oxime, combined with an insecticidal substance, afoxolaner. The aim of this literature work was to investigate how effective and safe this “combination” is against gastrointestinal nematodes in dogs.

    This study is a literature review. Articles were selected from PubMed article database, Primo and Science Direct after searches with different key terms. Through different combinations of keywords scientific articles that coordinated with the studies aim were selected for critical appraisal. A series of studies about efficacy of NexGard Spectra®  which were conducted in a wide range of different countries such as USA, South Africa and some countries in Europe have been analyzed. Five randomized double-blind studies are chosen as a basis for the thesis. Furthermore, an overview of the Swedish Board of Agricultures report on drugs sale for treatment of animals is also included.

    The results of the literature reviews show that NexGard Spectra®  chewable tablet, containing the two substances milbemycin oxime and afoxolaner, is a safe and effective treatment for dogs who are infected with a wide range of nematodes. No pharmacological interaction between the two active substances or serious negative influence on animal health has been reported. Detection of parasite occurrence has showed high efficacy of the product against most gastrointestinal nematodes.

    Conclusions that can be drawn from this study are that NexGard Spectra®  can be considered as a safe and effective treatment against gastrointestinal nematodes in dog. The fact that nematode infections in dogs could be prevented or treated by NexGard Spectra® can be just because of the endoparasitic substance, milbemycine oxim. Nevertheless, because NexGard Spectra®  is basically an anti endo- ectoparasite product, its efficacy against both endo- and ectoparasites requires better methods to analyze and determine efficacy of  NexGard Spectra® against both endo and ectoparasites and clearer guidelines to justify usage of it.

  • 320.
    Helin, Anu S.
    et al.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Biology and Environmental Science.
    Aarts, Lauren
    Linnaeus University, Faculty of Health and Life Sciences, Department of Biology and Environmental Science.
    Bususu, Isaya
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Andersson, Håkan S.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Rosengren, Johan
    University of Queensland, Australia‎.
    Chapman, Joanne R.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Biology and Environmental Science. University of Kansas, USA.
    Waldenström, Jonas
    Linnaeus University, Faculty of Health and Life Sciences, Department of Biology and Environmental Science.
    Antimicrobial activity differences in reduced vs. oxidized AvBD3b peptides in mallards (Anas platyrhynchos).2017Conference paper (Other academic)
  • 321.
    Helin, Anu S.
    et al.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Biology and Environmental Science.
    Aarts, Lauren
    Linnaeus University, Faculty of Health and Life Sciences, Department of Biology and Environmental Science.
    Bususu, Isaya
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Andersson, Håkan S.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Rosengren, Johan
    University of Queensland, Australia.
    Chapman, Joanne R.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Biology and Environmental Science.
    Waldenström, Jonas
    Linnaeus University, Faculty of Health and Life Sciences, Department of Biology and Environmental Science.
    Antimicrobial differences between AvBDs in mallards (Anas platyrhynchos)2018Conference paper (Other academic)
  • 322.
    Helin, Anu S.
    et al.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Biology and Environmental Science.
    Aarts, Lauren
    Linnaeus University, Faculty of Health and Life Sciences, Department of Biology and Environmental Science.
    Chapman, Joanne R.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Biology and Environmental Science.
    Andersson, Håkan S.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Waldenström, Jonas
    Linnaeus University, Faculty of Health and Life Sciences, Department of Biology and Environmental Science.
    Bactericidal tests of mallard (Anas plathyrynchos) ß-defensin alleles2017Conference paper (Other academic)
  • 323.
    Helin, Anu S.
    et al.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Biology and Environmental Science.
    Chapman, Joanne R.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Biology and Environmental Science. University of Kansas, USA.
    Tolf, Conny
    Linnaeus University, Faculty of Health and Life Sciences, Department of Biology and Environmental Science.
    Aarts, Lauren
    Linnaeus University, Faculty of Health and Life Sciences, Department of Biology and Environmental Science.
    Bususu, Isaya
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Rosengren, Johan
    University of Queensland, Australia.
    Andersson, Håkan S.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences. Uppsala University, Sweden;Karolinska Institutet, Sweden.
    Waldenström, Jonas
    Linnaeus University, Faculty of Health and Life Sciences, Department of Biology and Environmental Science.
    Relation between structure and function of three AvBD3b variants from mallard (Anas platyrhynchos)Manuscript (preprint) (Other academic)
    Abstract [en]

    Defensins are multifunctional antimicrobial peptides expressed in several tissue types and leucocytes as part of the innate immune response against microbes. Based on the three-dimensional structure and disulfide connectivity, vertebrate defensins are subdivided into α-, β-, and θ-defensins. While all three types have been found in mammals, only β-defensins have been identified in birds. Genetic studies have revealed dozens of different avian β-defensin (AvBD) genes in different bird species, as well as allelic variation for different genes. Knowledge of the relation between avian peptide structure features and antimicrobial activity is however limited. In this study, the structure-functional relations of three variants of AvBD3b, a mallard (Anas platyrhynchos) defensin of evolutionary interest, was investigated. Gene alleles encoding two of these peptides, AvBD3b:1 and AvBD3b:2 are common in mallards, whereas AvBD3b:3 occurs rare. These β-defensin peptides were synthesized as linear peptides and subjected to oxidative folding. The three-dimensional structure of AvBD3b:1, including disulfide bond connectivity, was determined using NMR, and those of AvBD3b:2 and AvBD3b:3 respectively, were modelled using AvBD3b:1 as the template. The antimicrobial activities of folded peptides were compared to those of linear peptides. The NMR analysis showed that folded AvBD3b adopts a three-dimensional structure typical for β-defensins, including C-terminal antiparallel β-sheets and disulfide bond organization between six cysteine (C) residues: C6-C34, C13-C28, and C18-C35. Analyses of antimicrobial activity showed that both folded and linear variants of the three peptides inhibited bacterial growth. However, differences in activity were observed, suggesting that folded AvBD3b:3 was the most efficient against both Gram-negative and Gram-positive bacteria. Taken together, these findings provide additional insight into the influence of amino acid sequence variation and three-dimensional structure on the antimicrobial activity of mallard AvBD3b.

  • 324.
    Helin, Anu S.
    et al.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Biology and Environmental Science.
    Chapman, Joanne R.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Biology and Environmental Science. University of Kansas, USA.
    Tolf, Conny
    Linnaeus University, Faculty of Health and Life Sciences, Department of Biology and Environmental Science.
    Andersson, Håkan S.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences. Uppsala University, Sweden;Karolinska Institutet, Sweden.
    Waldenström, Jonas
    Linnaeus University, Faculty of Health and Life Sciences, Department of Biology and Environmental Science.
    From genes to function: variation in antimicrobial activity of avian β-defensin peptides from mallardsManuscript (preprint) (Other academic)
    Abstract [en]

    Avian β-defensins are an important class of antimicrobial peptides in birds. These short cationic peptides are directly involved in the clearance of infections by membrane disruption, but can also act as immunomodulators and chemotactic agents recruiting immune cells. Recent genomic studies have shown the presence of several different avian β-defensin (AvBD) genes across the avian phylogeny, but also significant copy number variation and occurrence of pseudogenes. In mallard (Anas platyrhynchos) and other waterfowl AvBD genes are conserved and seem to be maintained by purifying selection. Due to their relatively simple peptide structure and direct mode of action, AvBDs is a potential tractable system to investigate how small differences in the gene sequence translates into differences in immune function. Here, we used genomic information from three different mallard defensin loci (AvBD4, AvBD10 and AvBD13) and synthesized the linear peptides from the most common allele of each locus, plus two rare alleles from AvBD13 locus and measured their antimicrobial activity against Gram-negative (E. coli and S. Typhimurium) and Gram-positive (S. aureus and M. luteus) bacteria. In these assays, AvBD4 showed the most potent antibacterial activity against both Gram-negative and Gram-positive bacteria, with an IC50 value of 0.48 mM against S. Typhimurium. Among AvBD13 peptides, the less frequently observed AvBD13:2 variant, was most potent, with IC50 value against S. aureus approximately 15 times lower than that of the most common AvBD13:1. Interestingly, AvBD10 had no antibacterial effect on the tested bacteria. Thus, antimicrobial function varied substantially among loci, but also within the AvBD13 locus, suggesting a direct link between genetic variation and immune function variation. Interestingly, results from assays with AvBD4 and AvBD13 seem to indicate that a higher positive net charge in peptides is associated with a more potent antibacterial effect.

  • 325.
    Hellsten, Janna
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Förekomst av Extended spectrum β-lactamase -producerande E.coli och K.pneumoniae hos måsfåglar i Spanien2019Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
  • 326.
    Henriksson, Julia
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Characterization of Composition of the Fat-rich Residues from Grease Separators2016Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    Fat, oil, and grease (FOG) deposits in wastewater systems reduce sewer diameter and can completely block the pipe, leading to sanitary sewer overflows (SSOs). This impacts both public health and the environment. Grease separators (GSs) are tanks that have the ability to prevent a substantial part of the incoming FOG from entering the sewer system. The aim of this study was to characterize the fatty acid profile and the change over time in fat content, free fatty acids (FFAs) and dry solids in FOG-rich residues from three GSs in the Stockholm region. One of these GSs was treated with a biological system (GOR BioSystem™). The results show a lower amount of fat and dry solids in the biologically treated GS compared with the two untreated. The proportion of FFAs is high from the beginning of the study period in grease caps from all GSs analyzed. The predominant fatty acids in FOG was in this study palmitic (C16:0), stearic (C18:0), oleic (C18:1) and linoleic acid (C18:2), which is consistent with previous studies. However, there was a higher content of palmitic acid (C16:0) and saturated fatty acids in the grease caps from the treated GS. The untreated GSs had a higher content of oleic acid (C18:1) and unsaturated fatty acid, which in one of these GSs decreased during the study period. In conclusion, the change in the fatty acid profile in FOG-rich residues did not follow the same pattern in the different GSs and the results were inconclusive. Further studies, with a longer time perspective, are needed in this area.

  • 327.
    Henriquez Monteagudo, Albert
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Denosumab jämfört med alendronat vid långtidsbehandling av osteoporos hos postmenopausala kvinnor2018Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    Background

    Osteoporosis is the most common skeletal disease in Scandinavia. About every other woman and every 4th man will suffer from some kind of fracture during their lifetime. With an aging population, the medical and socio-economic impact of osteoporosis, especially postmenopausal osteoporosis, will increase. The symptoms are pain in the legs, but in some cases the spine can be compressed, which causes a moderate backache. In Sweden, approximately 70,000 osteoporosis-related fractures occur annually. Estimated cost of SEK 3.5 billion. Of the 70,000 fractures annually, about 17,000 are hip fractures and 10,000 are vertebral fractures. Medicinal products used as first choice are bisphosphonates like alendronate in treatment for osteoporosis. Denosumab is used in patients who cannot take bisphosphonates.

    Aim

    The aim of the study was to compare the efficacies of alendronate and denosumab in preventing fractures and to examine the effects of long-term and short-term treatment of osteoporosis on bone mineral density (BMD) in post-menopausal women.

    Results

    When alendronate is used in the first 3 years compared with denosumab, BMD growth at the lumbar spine is almost the same. Alendronate gave a BMD increase of 8.8% after three years at the lumbar spine and denosumab a BMD increase of 9.2% at the lumbar spine. However, after three to five years of using alendronate, it begins to lose its effect on increasing BMD. In the first three years, the use of alendronate for preventing vertebral fractures gave a NNT (numbers needed to treat) = 33 and for nonvertebral fractures NNT = 45. For denosumab NNT = 20 for vertebral fractures and for nonvertebral fractures NNT = 50 in the first three years. After 10 years of use of alendronate, BMD increase at the lumbar spine was 13.7%, while denosumab resulted in a BMD growth of 18.4% after 8 years of use.

    Conclusion

    Alendronate is a good choice as a drug for the first three to five years. Alendronate is stored in the body and continued treatment does not have the same effect as the first few years. On the other hand, denosumab is a better alternative, as it results in continued BMD growth for up to 8 years of use. The problem is that denosumab is too expensive to give to everyone who has osteoporosis. Hopefully, in the future, biological medicines will become cheaper, so that more people can be treated with denosumab.

  • 328.
    Herbertsson, Jenny
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Utveckling eller konservatism? - Några nedslag i militära läkemedelslistor och farmakopéer med upptakt i Stormaktstiden.2018Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    Introduction: During the early part of The Swedish Empire the use of drugs came from the herbal galenica alignment. In the year 1663 the Collegium medicum are formed and the first pharmacopoeia is released, Pharmacopoeia Holmiensis Galeno-chymica. Ministry of Mining is formed in year 1637, where chemical drugs are prepared (chymica). Count Carl Gustav Wrangel orders an import in preparation for the polish war year 1655. Västmanland regiment got a drugdelivery year 1705, and a copy is preserved at the delivery. Carl von Linné and surgeon Kranert establishes druglists in the year of 1741 to be able to equip the navy for Hattarnas war. In the year of 1789 it is decided that the army and navy will be equipped with drugs according to a list in a series of militarypharmacopoeias. In the year of 1676 the warship Kronan wrecked outside the coast of Öland, in year 1980 the wreck is found and 2002 a unique chesat with drugs is also found in the wreck.

    Method: Raw materials and simple drugs, simplica, are listed in Excel. The substance content is listed for respective year, which gives a foundation for a database. The application of the Excel-database is exemplified with a number of drugs.

    Results: The percentage of paracelsian drugs is unchanged between the years of 1655-1834 with a percentage by 29-34,7 %. In year 1871 the percentage is 51,7 %. Of the three selected galenical substances, opium is the one that increases the most from 1789. Ipecacuanha radix is present from 1741 and Rhabarbari radix has a low occurrence. Of the three selected galenical substances the greatest increase is that of lead and mercury. Antimony is of a low occurrence, exept in the year of 1705. The percentage of paracelsian preparations is higher than the galenical from the year of 1741. The percentage of patch preparations is dominant, exept in the year of 1837. Discussion and conclusion: Opium have the highest increase of the galenical substances, morphine is avaliable from year 1871 in the listing of drugs. From 1871 the percentage paracelsian drugs is at 51, 7 %. New substances are presents like ether, phenol and morphine, which show that there has been a development based on the chemical advances during this timeframe.

  • 329.
    Hermansson Albien, Linda
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Varför blir inte barnen av med sina huvudlöss?2014Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [sv]

    Över hela världen anses huvudlusen (Pediculus humanus capitis) vara den vanligaste ektoparasiten hos människa. I Sverige säljs det ca 100 000 förpackningar med avlusningsmedel varje år, så problemet är uppenbart. Resistensutveckling hos huvudlöss tros vara en viktig orsak till ökningen av dessa parasiter. I maj 2010 kom Läkemedelsverket ut med nya behandlingsrekommendationer där medicintekniska produkter är förstahandsval. Malation respektive permetrin ligger på en tredje respektive fjärdeplats i denna rekommendation. Ivermektin är ett annat medel som har använts bland annat mot skabb men även som massbehandlingar i områden med låg socioekonomisk status.

    Syftet med denna studie var att undersöka effekten av dimetikon, malation, permetrin och ivermektin som behandling mot huvudlöss.

    Effekten av behandling av huvudlöss varierar mellan olika preparat. Andelen lusfria efter 1-2 behandlingar med dimetikon varierade mellan 60-97 %. För malation och permetrin varierade behandlingsutfallet mellan 33-85% respektive 12-67 %. Ivermektin visade sig vara mest effektiv (95 %) då det gavs som en oral dos på 400 µg/kg kroppsvikt. Effekten i samtliga studier mättes genom att bedöma hur många individer som var lusfria efter behandlingen. 

    Slutsatsen i detta arbete är att inget av de behandlingsalternativ som lyfts fram visar på hundraprocentig effektivitet. Den varierade effekten av malation och permetrin orsakas sannolikt av en ojämnt geografisk utbredd resistensutveckling runt om i världen. Dimetikon är ett bra alternativ då risken för resistensutveckling anses som låg och den har en god effekt mot huvudlöss.  Ivermektin kan vara ett alternativ vid svårbehandlade fall av huvudlöss men bör användas med försiktighet då redan resistensutveckling har påträffats hos skabb.

  • 330.
    Hillerhag, Johan
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Botulinumtoxin A mot kronisk migrän2017Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    Headache is a very common condition, and there are a number of variants of headache. About 90 % of all people in the world have experienced headache. Headache belongs to the group of diseases with the highest prevalence in the world but the disease is also largely under-diagnosed. Only 50 % of those who suffer from a headache disorder will have a diagnosis. Headaches can be divided into primary and secondary headaches. Common primary headaches are tension type headaches and migraines. The prevalence of migraine is approximately 15 % and is considered one of the 10 most common disabling disease in the world. Chronic migraine is a severe variant of migraine in which patients have at least 15 headache days per month during at least 3 months. Ordinary seizure medications such as triptans and NSAIDs can cause medical overuse headache and that’s why it is important to have effective prophylactic treatment. Since 2011 Botulinumtoxin A is approved in Sweden as a prophylactic treatment for chronic migraine.

     

    The aim of this study was to investigate the effectiveness of Botulinumtoxin A as a prophylactic treatment against chronic migraine. This literature study is based on results from five scientific articles. Articles were obtained from the database PubMed. In the first three articles Botulinumtoxin A was compared with placebo treatment and in the two remaining articles Botulinumtoxin A was compared with topiramate and amitriptyline. The results from this study show that Botulinumtoxin A is more effective than placebo for chronic migraine in terms of reducing the number of days with headache during a month and also reducing the number of episodes. The work has also shown that Botulinumtoxin A treatment is more effective than placebo in reducing the number of days with migraine. Botulinumtoxin A has also been shown to be as effective as amitriptyline and topiramate as prophylactic treatment for chronic migraine. Botulinumtoxin A also has fewer side effects than amitriptyline

  • 331.
    Hjelm, Carolina
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Patientens informationsunderlag för ordinerade läkemedel: I vilken utsträckning använder patienter sin lista ”Mina sparade recept på apotek” 2019Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    In 2017, there were 6.6 million of Sweden's population that retrieved at least one drug from the pharmacy. Today, drug treatment is becoming increasingly common both in the home and in the healthcare sector. Patients who have 5 drugs or more have an increased risk of lack of compliance in their drug therapy. The purpose of this study was to investigate which information base the patients use to keep track of their drug treatment and to what extent patients use the prescription list "My saved prescriptions at the pharmacy". Six pharmaceutical students conducted patient interviews at eight different pharmacies in Sundsvall, Fränsta, Härnösand and Stockholm.

    For the study, 167 patients were finally recruited and 55% used the "My saved prescriptions at the pharmacy". 13% used the drug list “My current medicines". 98% knew the list ""My saved prescriptions at the pharmacy ". At each pharmacy visit, 57 pharmacy customers had received the list printed from the pharmacy. The drug list "My current medicines" was used by 13% and the pharmaceutical list was used by 2%. The outcome for the 167 customers who participated in the study was that 26% felt that there were difficulties in keeping track of their drug treatment.

    Using the prescription list "My saved prescriptions at the pharmacy" as their basis is not the optimum when outdated prescriptions can be found, and that recipes can be missing which are current since the prescription validity is 12 months and then canceled and found among outdated prescriptions. The optimal basis should be the drug list "My current medicines" that each individual prescriber should update to the current version and also print it to their patient at each visit to reduce the risk of error medication.

  • 332.
    Holm, Jesper
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Effektivitet av tacrolimus jämfört med konventionell behandling vid atopisk dermatit hos vuxna och barn2016Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    Atopic dermatitis (AD) also known as eczema, is a chronic inflammatory skin disease, characterized by dry skin, itching and erythema. The prevalence of AD has been estimated between 10-20 % in children and 1-3 % in adults.

     In the early 1950s the anti-inflammatory group of drugs, topical glucocorticoids, were developed and have since been established as the golden standard for the treatment of AD. Long-term use of these drugs can lead to some serious side effects like chronic skin thinning. This has led to the development of new anti-inflammatory drugs, so called topical immunomodulators, containing the substances tacrolimus or pimecrolimus. Unlike topical glucocorticoids these drugs do not affect the collagen synthesis, and therefore do not cause any skin thinning.

    Tacrolimus is also a commonly used substance in drugs intended to reduce the activation of the immune system after organ transplantation. Long-term studies in this field have shown an increased risk of developing lymfoma and skin cancer. Because of the still unknown risk for topical use, the federal agency U.S. Food and Drug Administration (FDA) added a “black box” warning to its label. Therefore, tacrolimus has not replaced glucocorticoids as a first-line treatment of AD.

    This study analyzed a total of five clinical trials from the PubMed database, to examine tacrolimus efficacy and safety for short-term treatment. Four of these clinical trials compared tacrolimus with glucocoticoids in both adults and children. One of the clinical trials compared tacrolimus and pimecrolimus in adults. The results show that tacrolimus is at least equivalent or more effective than glucocorticoids and pimecrolimus, but it induces more short-term side effects like skin burning and intense itching on the treated area. In summary, tacrolimus is an effective drug to use in the short-term treatment of AD in both children and adults. Future long-term studies have to be made to evaluate the safety concern of cancer development. 

  • 333.
    Holm, Matilda
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Läkemedelsrelaterad hyponatremi: En beskrivning av mönster och trender bland spontanrapporterade biverkningar2014Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [sv]

    Introduktion: Hyponatremi kan orsakas av många läkemedel, exempelvis diuretika, antidepressiva och antiepileptika. Riskerna med hyponatremi är många och det är önskvärt att finna sätt att förebygga denna biverkan, t.ex. genom regelbundna kontroller av natriumvärdet. Vissa patientgrupper är extra känsliga för att utveckla hyponatremi och den här studien syftar till att urskilja mönster och gemensamma nämnare kring vilka patienter och läkemedel som finns representerade i rapporter om hyponatremi som biverkning. Metod: Studien gjordes genom sökning efter hyponatremi i databasen SWEDIS som innehåller spontana biverkningsrapporter från sjukvården. Sökningen begränsades till att omfatta rapporter som inkommit 2010-2013. Reslutat: Sökningen i SWEDIS genererade 288 rapporter varav 280 av dessa inkluderades och analyserades. 87% av biverkningarna bedömdes som allvarliga. Patienterna hade en klar övervikt mot de högre åldrarna; 96% var över 50 år. 76% av patienterna var kvinnor. De läkemedelsgrupper som misstänktes som orsak till hyponatremin i flest rapporter var SSRI (20%), Tiazidbesläktad diuretika och kaliumsparande medel (18%), Tiazider (15%) och Karboxamidderivat (13%). Bland kvinnorna var den vanligaste misstänkta orsaken läkemedel inom gruppen SSRI, medan läkemedel inom gruppen Karboxamidderivat var de vanligaste bland männen. 30% av rapporterna hade mer än ett misstänkt läkemedel. De vanligaste misstänkta läkemedlen förekom ofta i kombination med varandra. 37% av biverkningarna i rapporterna hade inträffat under sommarmånaderna juni-juli-augusti. Slutsatser: Kontroller av natriumnivån är extra viktigt för äldre personer som ordineras flera läkemedel som kan ge hyponatremi eller har andra sjukdomstillstånd som kan bidra till hyponatremi, speciellt under varma sommarperioder.

  • 334.
    Holmeland, Sofie
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Risken att utveckla venös tromboembolism: En jämförelse mellan två kombinerade preventivmedel som innehåller dienogest eller levonorgestrel.2017Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [sv]

    Kombinerade preventivmedel används för att förhindra graviditet. Dessa preventivmedel innehåller både östrogen och progesteron. Kombinerade preparat som innehåller levonorgestrel (LNG) rekommenderas i första hand för denna kombination ger minst risk att utveckla venös tromboembolism (VTE). LNG ges ofta i kombination med etinylestradiol (EE). Dienogest (DNG) är ett progesteron som säljs i Sverige i kombination med estradiolvalerat (E2V). Kombinationen säljs under produktnamnet Qlaira. Risken att få VTE med kombinerade preventivmedel som innehåller DNG är inte kartlagd än. Syftet med denna litteraturstudie var att undersöka om risken att få VTE med kombinerade preventivmedel som innehåller DNG är större jämfört med preventivmedel som innehåller LNG. Studier samlades från databasen PubMed och sökord som användes var ”dienogest VTE” och ”dienogest venous thrombosis”. Några av studierna hittades genom dessa sökord och resterande kunde hittas genom funktionen ”similar articles” på PubMeds hemsida. Fyra kliniska studier och två epidemiologiska studier ligger till grund för denna studie. Studierna jämförde kombinationspreparat som innehöll DNG eller LNG avseende risken att drabbas av VTE. Resultatet från de kliniska studierna visar att användarna av DNG/E2V och LNG/EE saknade statistiskt signifikanta (p>0,05) skillnader mellan varandra. Dock fanns det statistiskt signifikanta (p<0,05) skillnader mellan användarna av DNG/E2V och LNG/EE på intraindividuell nivå. Mellan användarna av DNG/EE och LNG/EE fanns det statistiskt signifikanta skillnader (p<0,05) mellan användargrupperna. Resultaten från de epidemiologiska studierna visade att det inte fanns någon statistiskt signifikant (p>0,05) skillnad mellan DNG/EE och LNG/EE angående risken att drabbas av VTE. Preparat med DNG ger, precis som alla kombinerade preventivmedel, en ökad risk att drabbas av VTE. Denna risk är jämförbar med kombinerade preparat som innehåller LNG. Risken att drabbas av VTE beror troligen på vilket östrogen som progesteronet är kombinerat med och om individen redan är utsatt för en större risk att drabbas av VTE. Studier med större behandlingsgrupper behövs för att undersöka ämnet ytterligare.

  • 335.
    Holmgren, Fanny
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Hur verkar passiv vaccinering vid Alzheimers sjukdom?2019Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [sv]

    Bakgrund: Det finns olika typer av demenssjukdomar och Alzheimers sjukdom (AD) är den vanligaste formen i Sverige. AD karakteriseras av att nervceller i hjärnan dör som leder till försämring av minne och kognitiva förmågor. Det är ungefär 100 000 personer i Sverige som lever med AD och det är vanligast hos äldre över 65 år. Eftersom genomsnittsåldern hos människor ökar i hela världen ökar även antalet människor som får sjukdomen. I nuläget finns det ingen behandling som botar AD utan endast läkemedel som dämpar symptomen. I ungefär två decennium har forskare studerat AD och utvecklat aktiv och passiv vaccinering med varierande resultat. Tanken är att passiv vaccinering ska minska Amyloid-beta (Aβ) plack som anses vara av stor betydelse för sjukdomsförloppet och stoppa fortsättningen av förloppet och förbättra de kognitiva förmågorna. Syfte: Syftet med detta examensarbete var att redogöra för rådande utvecklingsläge vid framtagandet av antikroppsbaserad terapi vid AD. Utifrån syftet ställdes tre frågeställningar upp. Frågeställning 1: Hur fungerar passiv vaccinering vid AD? Frågeställning 2: Hur tidigt behöver en behandling med passiv vaccinering sättas in vid AD och är det några personer som speciellt ska få behandling? Frågeställning 3: Vilken potential har passiv vaccinering vid AD och kommer behandlingen att bota AD? Metod: Detta examensarbete är en litteraturstudie baserad på 6 vetenskapliga artiklar. Resultat: Samtliga musstudier visade uppfylla sina syften. Alla tre antikropparna visade en effektiv penetration till hjärnan och effektiv reduktion av Aβ plack nivån. För Fas 1-studierna erhölls antikropparna vara säkra och väl tolererade hos människor upp till specifika doser. Antikropparnas förmåga att förbättra de kognitiva förmågorna hos människorna studerades via Mini-Mental State Examination (MMSE) där alla tre studierna presenterade ett MMSE värde före start av behandling men ingen Fas 1-studie presenterade MMSE värdet efter behandling, vilket betyder att antikropparnas förmåga att förbättra kognitiva förmågor inte har presenterats i dessa studier. Slutsats: Alla tre antikroppar studeras just nu i Fas 3-studier och förväntas att avslutas 2022- 2023. Det är fortfarande oklart om passiv vaccinering kommer att fungera för att bota AD. Studierna visar en reduktion av Aβ plack, dock är det viktigt att poängtera att studiegrupperna är små och studierna är sponsrade av läkemedelsföretagen. Läkemedelskandidaterna kan förhoppningsvis tillsammans med stamcellsterapi och anti-ag

  • 336.
    Holt, Margrethe
    et al.
    Univ Oslo, Norway;Oslo Univ Hosp, Norway.
    Seim, Bjorn E.
    Univ Oslo, Norway;Oslo Univ Hosp, Norway.
    Ogaard, Jonas
    Oslo Univ Hosp, Norway.
    Olsen, Maria B.
    Oslo Univ Hosp, Norway.
    Woldbaek, Per R.
    Oslo Univ Hosp Ulleval, Norway.
    Kvitting, John-Peder Escobar
    Oslo Univ Hosp, Norway.
    Aukrust, Pal
    Univ Oslo, Norway;Oslo Univ Hosp, Norway.
    Yndestad, Arne
    Univ Oslo, Norway;Oslo Univ Hosp, Norway.
    Mollnes, Tom Eirik
    Univ Oslo, Norway;Oslo Univ Hosp, Norway;Nordland Hosp, Norway;Univ Tromsø, Norway.
    Nilsson, Per H.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences. Univ Oslo, Norway.
    Louwe, Mieke C.
    Oslo Univ Hosp, Norway.
    Ranheim, Trine
    Univ Oslo, Norway;Oslo Univ Hosp, Norway.
    Selective and marked decrease of complement receptor C5aR2 in human thoracic aortic aneurysms: a dysregulation with potential inflammatory effects2019In: Open heart, E-ISSN 2053-3624, Vol. 6, no 2, p. 1-8, article id e001098Article in journal (Refereed)
    Abstract [en]

    Objective The aetiology of thoracic aortic aneurysm (TAA) is largely unknown, but inflammation is likely to play a central role in the pathogenesis. In this present study, we aim to investigate the complement receptors in TAA. Methods Aortic tissue and blood from 31 patients with non-syndromic TAA undergoing thoracic aortic repair surgery were collected. Aortic tissue and blood from 36 patients with atherosclerosis undergoing coronary artery bypass surgery or aortic valve replacement were collected and served as control material. The expression of the complement anaphylatoxin receptors C3aR1, C5aR1 and C5aR2 in aortic tissue were examined by quantitative RT-PCR and C5aR2 protein by immunohistochemistry. Colocalisation of C5aR2 to different cell types was analysed by immunofluorescence. Complement activation products C3bc and sC5b-9 were measured in plasma. Results Compared with controls, TAA patients had substantial (73%) downregulated gene expression of C5aR2 as seen both at the mRNA (p=0.005) level and protein (p=0.03) level. In contrast, there were no differences in the expression of C3aR1 and C5aR1 between the two groups. Immunofluorescence examination showed that C5aR2 was colocalised to macrophages and T cells in the aortic media. There were no differences in the degree of systemic complement activation between the two groups. Conclusion Our findings suggest downregulation of the C5aR2, regarded to act mainly anti-inflammatory, in electively operated TAA as compared with non-aneurysmatic aortas of patients with aortic stenosis and/or coronary artery disease. This may tip the balance towards a relative increase in the inflammatory responses induced by C5aR1 and thus enhance the inflammatory processes in TAA.

  • 337.
    Hommerberg, Louise
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Behandling av HER2-positiv bröstcancer med den monoklonala antikroppen trastuzumab: En undersökning av behandlingens effektivitet och säkerhet2018Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    Breast cancer is one of the most common types of cancer in Sweden, with over 8000 patients diagnosed every year. Since 1960 the survival rate for breast cancer has climbed over 30 % and is still rising. There could be several reasons for this development. One reason could be the more effective screening programs implemented into the Swedish health care system, which allows the cancer to be found and treated at an early stage of the disease. Early treatment is one of the key factors in treatment success. Another reason is the development of more efficient targeted cancer therapies that are now used to treat breast cancer. One of the new diagnostic tools that are used in the diagnosing of breast cancer is classification of intrinsic subtype. This analysis serves to discover specific proteins and receptors that are overexpressed in the tumour cells, and that could act as potential drug targets. One such receptor is the Human Epidermal Growth Factor Receptor 2 (HER2). The HER2 is a tyrosin kinase receptor which upon activation plays a major role in cell growth and cell division. In approximately 20-30 % of all breast cancers the expression of this receptor on the cell surface and/or the gene coding for the receptor is drastically amplified. This amplification is one of the factors that allow the tumour cells to grow and divide almost unlimitedly. The extreme potency of this receptor makes the HER2-positive breast cancer one of the most aggressive breast cancer types there is. By identifying this receptor as a major cause of the cancer research has allowed the development of a very specific targeted therapy in the form of the monoclonal antibody trastuzumab. Trastuzumab binds to the HER2-receptor and inhibits its growth stimulating effects. For several years it has been used to treat patients with HER2-positive breast cancer. However, to some extent the optimal treatment regimen is still unknown. The aim of this study was therefore to evaluate the current treatment regimen of HER2-positive breast cancer with trastuzumab. The evaluation will be based on analysis of the treatments’ efficacy, safety and optimal treatment duration.

     

    This is a literature study based on the analysis of five clinical trials that were collected using the medical an bioscientific database PubMed. The search was limited to only include studies that analysed the use of trastuzumab as adjuvant treatment for early HER2-positive breast cancer. Studies that analysed the effect in metastatic breast cancer were excluded to enable a more specific analysis. The studies that were selected analysed efficacy and/or treatment duration as primary end points and safety as a secondary end point or as a part of the primary endpoint. Based on the results presented in these studies trastuzumab is an effective and safe treatment of choice for early HER-2 positive breast cancer. The studies also showed evidence to support the current recommended treatment duration of 12 months. The safety analysis showed that trastuzumab is a generally well tolerated treatment; however as with any cancer treatment there are certain risks, cardiac toxicity being the most serious. In conclusion, this literature study supports the current treatment regimen with trastuzumab for HER2-positive breast cancer.

  • 338.
    Huang, Shan
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Interaction between biomaterials and innate immunity with clinical implications2015Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Today there is an increasing clinical demand and expectation of patients for biomaterials, which underscores the importance of discovering the correlations between biomaterials and biological systems, especially blood. When an artificial material makes contact with blood, the first event is a rapid adsorption of plasma protein on the material surface, on top of which the innate immune system is triggered, with potentially detrimental consequences. The work presented in this thesis, reported in four papers, was designed to investigate complications associated with (a) biomaterial-induced immune systems, including activation mechanisms and crosstalk between cascades on the biomaterial surface, and with (b) clinical investigations.

    In Paper I and Paper II, a series of studies led to the development of a direct prediction of the subsequent biological events based on the pattern of initially bound proteins. A reciprocal relationship was demonstrated between activation of the contact system and the complement system when they were induced on artificial material surfaces. Based on these studies, a robust and simple method for biocompatibility testing was proposed and validated, yielding high specificity and sensitivity when compared to today’s gold standard. Paper III investigated biomaterial-induced activation of complement and leukocytes in dialysis treatment-related conditions. The results suggested that citrate is more biocompatible than the conventionally used acetate. This reduction in activation could be further enhanced with higher citrate concentrations, suggesting that dialysis fluid containing citrate is a promising alternative to acetate dialysis fluid. Paper IV investigated complement initiation mechanisms with clinical implications. An experimental system was set up to revisit the initiation of the complement alternative pathway, and correlations were found between chaotropic or nucleophilic agents and iC3 generation under physiologically relevant conditions. A clinical study of hepatic encephalopathy patients indicated a direct correlation between elevated plasma ammonia and iC3 formation, as well as with complement activation in vivo

    Taken together, these studies have provided a model for a robust biomaterial test and have investigated biomaterial-induced complications in the fluid phase in clinically related conditions; furthermore, the basic mechanisms of complement activation have been dissected in relation to disease symptoms.

    Keywords: Complement system, contact system, blood, biomaterials, biocompatibility, in vitro screening, iC3, dialysis

  • 339.
    Huang, Shan
    et al.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Engberg, Anna E.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences. University and Regional Laboratories Region Skåne.
    Jonsson, Nina
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences. Uppsala University.
    Sandholm, Kerstin
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Nicholls, Ian A.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences. Uppsala University.
    Mollnes, Tom Eirik
    Oslo University Hospital Rikshopsitalet, Norway;University of Oslo, Norway;Nordland Hospital, Norway; University of Tromsø, Norway;Norwegian University of Science and Technology, Norway.
    Fromell, Karin
    Uppsala University.
    Nilsson, Bo
    Uppsala University.
    Nilsson Ekdahl, Kristina
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences. Uppsala University.
    Reciprocal relationship between contact and complement system activation on artificial polymers exposed to whole human blood.2016In: Biomaterials, ISSN 0142-9612, E-ISSN 1878-5905, Vol. 77, p. 111-119Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Inappropriate and uncontrolled activation of the cascade systems in the blood is a driving force in adverse inflammatory and thrombotic reactions elicited by biomaterials, but limited data are available on the activation of the contact system by polymers and the present study was undertaken to investigate these mechanisms in established models.

    METHODS: Polymer particles were incubated in (1) EDTA-plasma (10 mM) to monitor the adsorption of 20 selected proteins; (2) lepirudin-anticoagulated plasma to evaluate contact system activation, monitored by the formation of complexes between the generated proteases factor[F]XIIa, FXIa and kallikrein and the serpins C1-inhibitor [C1INH] and antithrombin [AT]; (3) lepirudin-anticoagulated whole blood to determine cytokine release.

    RESULTS: Strong negative correlations were found between 10 cytokines and the ratio of deposited FXII/C1INH, generated FXIIa-C1INH complexes, and kallikrein-C1INH complexes. Formation of FXIIa-C1INH complexes correlated negatively with the amount of C3a and positively with deposited IgG.

    CONCLUSIONS: A reciprocal relationship was found between activation of the contact system and the complement system induced by the polymers studied here. The ratios of FXII/C1INH or C4/C4BP, adsorbed from EDTA-plasma are useful surrogate markers for cytokine release and inflammatory response to materials intended for blood contact.

  • 340.
    Huang, Shan
    et al.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Sandholm, Kerstin
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Jonsson, Nina
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences. Uppsala University.
    Nilsson, Anders
    Gambro Lundia AB.
    Wieslander, Anders
    Gambro Lundia AB.
    Grundström, Gunilla
    Gambro Lundia AB.
    Hancock, Viktoria
    Gambro Lundia AB.
    Nilsson Ekdahl, Kristina
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences. Uppsala University.
    Low concentrations of citrate reduce complement and granulocyte activation in vitro in human blood2015In: Clinical Kidney Journal, ISSN 2048-8505, E-ISSN 2048-8513, Vol. 8, no 1, p. 31-37Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:The use of acetate in haemodialysis fluids may induce negative effects in patients including nausea and increased inflammation. Therefore, haemodialysis fluids where acetate is substituted with citrate have recently been developed. In this study, we investigated the biocompatibility of citrate employing concentrations used in haemodialysis.

    METHODS:The effects of citrate and acetate were investigated in human whole blood in vitro under conditions promoting biomaterial-induced activation. Complement activation was measured as generation of C3a, C5a and the sC5b-9 complex, and granulocyte activation as up-regulation of CD11b expression. For the experimental set-up, a mathematical model was created to calculate the concentrations of acetate and citrate attained during haemodialysis.

    RESULTS:Citrate reduced granulocyte activation and did not induce higher complement activation compared with acetate at concentrations attained during haemodialysis. Investigating different citrate concentrations clearly showed that citrate is a potent complement inhibitor already at low concentrations, i.e. 0.25 mM, which is comparable with concentrations detected in the blood of patients during dialysis with citrate-containing fluids. Increased citrate concentration up to 6 mM further reduced the activation of C3a, C5a and sC5b-9, as well as the expression of CD11b.

    CONCLUSIONS:Our results suggest that citrate is a promising substitute for acetate for a more biocompatible dialysis, most likely resulting in less adverse effects for the patients.

  • 341.
    Huang, Shan
    et al.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Sandholm, Kerstin
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Jonsson, Nina
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Rorsman, Fredrik
    Uppsala University Hospital.
    Nilsson, Bo
    Uppsala University.
    Nilsson Ekdahl, Kristina
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences. Uppsala University.
    An assay to monitor in vitro generation of non-proteolytically activated C3 in human plasmaManuscript (preprint) (Other academic)
  • 342.
    Huang, Shan
    et al.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Sandholm, Kerstin
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Nilsson, Bo
    Uppsala University.
    Nilsson Ekdahl, Kristina
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences. Uppsala University.
    iC3 generation elicited by the presence of ammonia and urea in human plasma2015In: Molecular Immunology, ISSN 0161-5890, E-ISSN 1872-9142, Vol. 67, no 1, p. 145-145Article in journal (Other academic)
  • 343.
    Huber-Lang, Markus
    et al.
    Univ Hosp Ulm, Germany.
    Nilsson Ekdahl, Kristina
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences. Uppsala University.
    Wiegner, Rebecca
    Univ Hosp Ulm, Germany.
    Fromell, Karin
    Uppsala University.
    Nilsson, Bo
    Uppsala University.
    Auxiliary activation of the complement system and its importance for the pathophysiology of clinical conditions2018In: Seminars in Immunopathology, ISSN 1863-2297, E-ISSN 1863-2300, Vol. 40, no 1, p. 87-102Article, review/survey (Refereed)
    Abstract [en]

    Activation and regulation of the cascade systems of the blood (the complement system, the coagulation/contact activation/kallikrein system, and the fibrinolytic system) occurs via activation of zymogen molecules to specific active proteolytic enzymes. Despite the fact that the generated proteases are all present together in the blood, under physiological conditions, the activity of the generated proteases is controlled by endogenous protease inhibitors. Consequently, there is remarkable little crosstalk between the different systems in the fluid phase. This concept review article aims at identifying and describing conditions where the strict system-related control is circumvented. These include clinical settings where massive amounts of proteolytic enzymes are released from tissues, e.g., during pancreatitis or post-traumatic tissue damage, resulting in consumption of the natural substrates of the specific proteases and the available protease inhibitor. Another example of cascade system dysregulation is disseminated intravascular coagulation, with canonical activation of all cascade systems of the blood, also leading to specific substrate and protease inhibitor elimination. The present review explains basic concepts in protease biochemistry of importance to understand clinical conditions with extensive protease activation.

  • 344.
    Hussain, Sara
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Hur har arbetsmiljön på apoteken påverkats av omregleringen av apoteksmarknaden?2013Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [sv]

    1 juli 2009 avreglerades det svenska apoteksväsendet från att ha varit statligt ägt. Avregleringen har även lett till att man numera får sälja ett urval av receptfria läkemedel i dagligvaruhandeln. Avreglering av apoteksmarknad har tidigare skett i Norge, Danmark och Island.Syftet med detta examensarbete var att undersöka hur och i vilken omfattning apotekspersonal anser att deras arbetsmiljö har påverkats av omregleringen. För att besvara frågeställningen har tre intervjuer gjorts med personer ur olika personalkategorier på apotek (en apotekschef, en receptarie och en apotekstekniker), och genom utdelning av enkäter till apotek i södra Stockholm. Av 70 utlämnade enkäter insamlades 32 ifyllda från 11 apotek i södra Stockholm.Intervjuerna gav olika utfall. Chefen var i stort sett nöjd med allt efter omregleringen, men både farmaceuten och teknikern såg negativa effekter av omregleringen i form av ökad stress, högre krav från chefen och sämre möjligheter att förlägga semester till sommarmånaderna. Resultatet från enkäten visar också att många är missnöjda med att de inte får ta ut en längre sammanhängande semester på sommaren. Dessutom har stressen ökat på arbetsplatsen efter omregleringen på grund av bland annat personalminskningen. Däremot lever de flesta cheferna upp till regeln om att arbetsdagen inte ska vara längre än 10 timmar.25 personer av 32 (78 %) har svarat att de antigen är nöjda eller varken eller med arbetsmiljön. Det är en relativ hög siffra med tanke på alla skriverier om försämrad arbetsmiljö på apoteken

  • 345.
    Hämäläinen, Sanna
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Apotekskunders informationsunderlag för att hålla reda på ordinerad läkemedelsbehandling2018Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    Background

    If patients have access to an adequate and updated list of prescribed drugs it will lead to reduced risk of medication error and thus to better quality of life at the individual level, as well as reduced public spending for medical care.

    In drug treatment, patient compliance is extremely important, as incorrect medical use can lead to severe consequences. For patients prescribed long-term treatment with drugs, compliance is estimated to be only 50% [1].

    There are several different sources patients can utilize to keep updated with their prescribed drugs;

    • The Medication List (ML) from the physicians’ electronic medical record[14].

    • The Prescription List (PL) with all prescriptions stored in the Swedish National

      Prescription Repository (NPR) accessible from any pharmacy in Sweden [19].

    • The Pharmacy Record List (PR) of the purchases on prescriptions made over the

      past 15-month period[15].

    • Paper prescriptions[20].

    • The pharmacy packaging labels[11].

      Patients may also access their PL over the internet.

    Objective

    The purpose of the study was to investigate, via questionnaire interviews in pharmacies, what sources of information customers used to keep updated in their prescribed drugs. Patients with at least five or more prescription drugs (data from the NPR) were included in the survey.

    It was also investigated how many customers that had knowledge of and had received a printout of the PL "My stored prescription at the pharmacy" at visits in the pharmacies.

    It was also investigated to what extent customers had visited a public website, through personal login, to take part of their PL, and how often.

    Methods

    This survey is a follow-up of another study "Patients' information on their prescribed current treatment" published in 2012 [25].

    In this study customers were recruited from 8 different pharmacies in Sweden. Customers where asked to answer questions from a questionnaire and a drug reconciliation was done. A total of 167 customers, with at least five prescribed drugs, were included.

    Key findings

    The majority, 55%, stated that they used the PL printout "My stored prescription at the pharmacy". 39% relied on instructions given on the of drug packages and the pharmacy labels with dosage instructions. 13% of the customers reported that they used the ML handed over from their physician. 8% stated that they used the website via personal login with e-ID to get to the PL ”My stored prescription at the pharmacy”.

    Conclusion

    On March 1, 2018, the government decided on the draft bill for a national pharmaceutical list. The list should provide a complete and up-to-date picture of the individual patient's drugs, regardless of who prescribed the drug and where in the country this occurred[19]. Thus, modernity development should lead to a reduced necessity of using several different sources for prescribed drugs, which can hopefully reduce the risk of errors in drug use and increase the overall patient safety.

  • 346.
    Håkansson, Andreas
    et al.
    Kristianstad University.
    Andersson, Håkan S.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Granfeldt, Yvonne
    Lund University.
    Diet inequality prevails among consumers interested and knowledgeable in nutrition2015In: Food & Nutrition Research, ISSN 1654-6628, E-ISSN 1654-661X, Vol. 59, article id 27601Article in journal (Refereed)
    Abstract [en]

    Previous studies have demonstrated a correlation between diet cost and adherence to nutritional recommendations among consumers in general. This has adverse effects on diet and health inequality. It could be hypothesized that consumers knowledgeable in nutrition escape this correlation

  • 347.
    Håkansson, Johanna
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Vaccination mot Humant Papillomvirus - vem bör vaccineras?2013Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    Background: Infection with Human Papillomavirus, HPV, is one of the world's most common sexual transmitted infections. The virus causes genital warts (condyloma) but certain virus types can cause cancer. The most common cancer type caused by the virus is cancer of the cervix. Nowadays there is a screening program for women between 23 and 60 years of age where Pap smears of the cervix is taken to discover abnormalities at an early stage. Cervical cancer is very common all over the world and this screening program saves many lives, but not in the less developed countries since the screening program is too expensive. A vaccine has been developed against the four most common HPV- types 6, 11, 16 and 18, and the vaccine costs less than the screening program, so it is now possible to save lives worldwide. The vaccine contains virus-like particles, VLP's, synthesized by L1-proteins from HPV types 6, 11, 16 and 18. HPV 6 and 11 are associated with the sexual transmitted disease condyloma, and HPV 16 and 18 can cause cancer in the cervix among women, but also other kinds of anogenital cancer types. Today, the HPV vaccine is included in the general vaccination program for girls in 5th and 6th grade in Sweden, but not for boys. The risk to get infected with the virus is equal between girls and boys and this has raised the question whether or not boys should be included in the general HPV-vaccination program as well.

    Purpose: The aim of this study was to evaluate whether or not there is evidence that suggest vaccinating other populations than young girls.

    Methods: The study is a literature study of clinical trials collected from the database PubMed.

    Results: Many clinical trials, where the vaccine efficacy among young initially HPV-naive girls have been evaluated, have been performed. They show that the vaccine is effective in preventing HPV-infection in this population. In a population with older participants, that have been sexually active and, thereby, are likely to have been infected with the virus, the vaccine's efficacy is more unknown. Clinical trials have been made in populations like this, with participants with initially unknown HPV-status, and the vaccine shows efficacy against infection with the HPV type, or types, that the individual is not already infected with. Clinical trials have also been made among boys and young men and the vaccine's efficacy is noninferior among men compared with the vaccine efficacy among girls and young women.

    Conclusions: Those findings support the inclusion of boys in the general vaccination program. They also show that already infected individuals can take benefit from the vaccine since it is not very likely that they are infected with all four vaccine types. But, before a gender neutral vaccination can be recommended, and before vaccination of already infected individuals is suggested, more and larger studies must be made. The new trials should also have longer follow up-times to determine whether a refill vaccination in the future will be needed.

  • 348.
    Håkansson, Malin
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    En jämförelse mellan apixaban och warfarin med fokus på profylaktisk effekt, säkerhet samt kostnadseffektivitet hos patienter med förmaksflimmer2016Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
  • 349.
    Hård, Julia
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Långvarigt bruk av alkohol ger kramper och epilepsi: Ett arbete om alkohols effekter på hjärnan2017Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    Alcohol has been used for drinking for many years and is a substance that is well known to most teenagers and adults. Most people also know that alcohol, when misused, can cause damage to both the liver and the kidneys but not as many people know about the damage alcohol can cause the brain. The damage that alcohol causes in the brain can lead to conditions where the patient can experience seizures, whitch can further devlop into epilepsy.

    Alcohol has different effects on the body. An immidiate response to alcohol is that the inhibitory signaling in the brain increases and the excitatory signaling decreases. When it comes to a prolonged misuse of alcohol the effects on the brain are the opposite and it can also increase the tolerance for alcohol. Inhibitory and excitatory signaling in the brain are essential and disturbance of those signals can be very damaging to the brain. The damages can develop and become permanent and it can also trigger different kinds of seizures. The seizures can in turn become very serious and fatal.

    Studies on the connection between alcohol and epilepsy has been conducted by Samokhvalov et al. (2010), Devetag et al. (1983), Bråthen et al. (1999), Tartara et al. (1983), Bartolomei et al. (1997), Victor och Brausch (1967) och Hillbom (1980) and have shown different results. The results however have shown a clear correlation between alcohol and epilepsi. In the study performed by Devetag et al. (1983) 58 % of 153 patients experienced seizures not related to alcohol withdrawl, alcohol induction or injury/disease. Of 60 patients who presented seizures in the study conducted by Bartolomei et al. (1997), 30 (50 %) had seizures not related to alcohol withdrawl, alcohol induction or injury/disease. A study performed by Bråthen et al. (1999) showed  16 patients (36 %) of 142 with seizures not related to alcohol withdrawl, alcohol indiction or injury/disease. Furthermore, a study conducted by Tartara et al. (1983) showed 30 patients with seizures, where 3 (10 %) of them were not related to alcohol withdrawl, alcohol induction or injury/disease.

    Seizures not related to alcohol withdrawl, alcohol abuse or injury/disease are difficult to investigate. Many scientists have tried to get insight in as to how alcohol can influence the ethiopathogenesis of epilepsy. What is alcohol-related seizures, what is the cause behind the seizures and how does one decide if the seizures can be defines as epilepsy.

    This literature review investigates the link between alcoholism and epilepsy to better understand this connection. The question of issue was ”if prolonged misuse of alcohol can lead to epilepsy” and to unravel the question, 7 studies were used. The studies main focus was alcoholism and seizures.

    The results from the studies indicated in total that alcohol prabably can cause epilepsy since none of the studies showed the opposite. A prolonged misuse of alcohol can lead to seizures and even epilepsy, but how this comes to be is not clear and needs to be properly investigated. Not to forget, some people who misuse alcohol do not get epilepsy and some never experience even a single seizure.

  • 350.
    Ignjic, Ljubica
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Vildagliptins effekt på kardiovaskulära riskfaktorer hos typ 2-diabetespatienter2019Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [sv]

    Diabetes mellitus är en av Sveriges största folksjukdomar och beräknas drabba omkring 5% av Sveriges befolkning där 85–90 % av de drabbade utgörs av typ-2 diabetes. Globalt beräknas de drabbade svara upp mot 500 miljoner och siffran fortsätter att stiga. Diabetes delas främst i typ 1 och typ 2-diabetes där typ 1 innebär förstörda betaceller och avtagen insulinproduktion medan typ 2 innebär nedsatt insulinkänslighet med avtagande betacellsfunktion. Orsak till diabetes mellitus tros vara genetisk dock finns det tydliga kopplingar mellan typ 2-diabetes och livsstil. Gemensamt för båda typerna är hyperglykemi. Typ 2 är direkt kopplat till hjärt-och kärlsjukdomar och behovet att ett glukossänkande preparat med skyddande effekt på hjärta och kärl är eftertraktat. Livsstilsförändring är alltid första steget i behandling av typ 2-diabetes och vid otillräcklig effekt tillkommer farmakologisk behandling där metformin alltid är förstahandspreparatet. Vid otillräcklig effekt med metformin eller kontraindikation ges natrium-glukos-kotransportör-2-hämmare, sulfonureider, glitazoner och/eller inkretinbaserade preparat som dipeptidylpeptidas 4-hämmare och/eller insulin. Denna studies syfte är att undersöka om dipeptidylpeptidas 4-hämmare vildagliptin har en skyddande effekt mot utveckling av kardiovaskulära komplikationer hos patienter med typ 2-diabetes. För att besvara frågeställning valdes 5 olika studier i databasen PubMed där vildagliptin jämfördes med andra plasmaglukossänkande agenter. Studiens slutsats är att vildagliptin inte har en uttalad effekt på kardiovaskulära komplikationer hos typ 2-diabetikerna även då den har en dämpande effekt på de inflammatoriska och glykemiska markörerna hsCRP, TNF-1, IL -1 och SDF-1. Vildagliptin i kombinationsterapi har en sänkande effekt på HOMA-IR, HOMA-, MAGE, FPPr och kan rekommenderas som behandling till typ 2- diabetiker med fokus på glukoskontroll. Association mellan blodglukos, insulin och inflammation är direkt relaterad till diabetes och kardiovaskulära komplikationer och intresset för vidare undersökning av dess association är stor.

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