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Austreid, Ingunn (Master thesis; Mastergradsoppgave, May-2008)[+][-]
Abstract: Studies have shown that fatty acids from fish and fish oils, like eicosapentaenoic acid (EPA) and docosapentaenoic acid (DHA) may have a beneficial role in cancer by inhibiting proliferation or inducing apoptosis of the cancer cells. Several mechanisms involving different metabolites (eicosanoids) of the fatty acids have been suggested for the anti-cancer actions, but the detailed effects are still not known. One of the eicosanoid groups of the fatty acids are epoxy-EPAs. Little have been investigated about epoxy-EPAs’ effect on cancer cells. This experiment is based on previous studies from this laboratory that have shown an anti-proliferative effect of epoxy-EPA on murine endothelial cells (unpublished data). In this study the effect of 8,9-epoxy-EPA was tested on human breast cancer cell line MDA-MB-231. The epoxide was tested alone and in combination with an epoxide hydrolase inhibitor, N’N-dicycyclohexylurea (DCU). Different cell viability assays were assessed to investigate the effect of 8,9-epoxy-EPA on cancer cell proliferation. Cell cycle and immunoblotting were carried out to test if cell cycle regulatory proteins were affected. 8,9-epoxy-EPA was found to increase cell viability of MDA-MB-231. No change in cell cycle regulatory proteins was found. 8,9-epoxy-EPA was also tested on the MDA-MB-231 cells together with a well known anti-cancer drug, paclitaxel. Cell viability assay and cell cycle analysis were assessed. An increase in cell viability of cell treated with both 8,9-epoxy-EPA and paclitaxel compared to cell treated with paclitaxel alone was found. No effect of 8,9-epoxy-EPA on cell cycle was observed. Results from these experiments are not what we expected based on previous studies. Further studies on cell mechanism and apoptosis are required to investigate possible differences in cell response to epoxide n-3 fatty acids. URI: http://hdl.handle.net/10037/1572 File(s) in this item: 1
thesis.pdf (1.089Mb) -
Dahlheim, Anne-Helene (Master thesis; Mastergradsoppgave, May-2008)[+][-]
Abstract: ABSTRACT Epidemiologic studies have indicated that n-3 polyunsaturated fatty acids (PUFAs) supplementation may reduce the incidence of breast cancer, also in vivo and in vitro studies have shown that n-3 PUFAs have an inhibitory effect on breast cancer cells. One important n-3 PUFA are eiocosapentaenoic acid (EPA), which are metabolized to five regioisomeric epoxyeicosatetraenoic acids (epoxy-EPAs) by the cytochromes P450 system. Further, these epoxides are metabolized by epoxide hydrolase (EH), which can be inhibited by N, N`-dicyclohexylurea (DCU), an epoxide hydrolase inhibitor (EHI). The effect of these five epoxy-EPAs and the combination of epoxy-EPAs and EHI on breast cancer cells is not known. In this study the effect of 8, 9-epoxy-EPA on the human estrogen responsive breast cancer cell line MCF-7 was tested. MCF-7 cells were treated with 8, 9-epoxy-EPA, DCU and a combination of 8, 9-epoxy-EPA + DCU. Both the treatment with 8, 9-epoxy-EPA and the combination of 8, 9-epoxy-EPA + DCU inhibited the growth of MCF-7 cells in the presence of FBS. Treatment with 8, 9-epoxy-EPA in the absence of FBS did not result in a change in cell viability, which indicates that the growth inhibition on MCF-7 cells by 8, 9-epoxy-EPA requires an additional proliferative stimulus. To examine the effects of 8, 9-epoxy-EPA on MCF-7 cell growth flow cytometry was used to monitor cell cycle progression. Cells treated with 8, 9-epoxy-EPA and the combination of 8, 9-epoxy-EPA + DCU for 16 and 24 hours were found to be arrested in G0/G1-phase, and did not progress through the cell cycle at the same rate as control cells. 8, 9-epoxy-EPA treatment for 24 hours also resulted in a corresponding decrease in G2/M-phase. The adding of DCU did not enhance the effect of the 8, 9-epoxy-EPA treatment on cell cycle progression significantly. Treatment in the absence of FBS showed no alteration in the progression of the cell cycle. The growth inhibition effect on MCF-7 cells of 8, 9-epoxy-EPA was further studied by examining changes in expression of different cell cycle regulatory proteins. The protein levels were found to be unaltered after 8, 9-epoxy-EPA treatment. The growth inhibition effect may be due to increased cell apoptosis as an alternative to decreased proliferation in MCF-7 cells. This possibility should be evaluated in further studies. URI: http://hdl.handle.net/10037/1574 File(s) in this item: 1
thesis.pdf (2.001Mb) -
Zabihyan, Behnaz (Master thesis; Mastergradsoppgave, May-2008)[+][-]
Abstract: BACKGROUND: Dyslipidaemia is more frequent in solid organ transplant recipients than in the general population. In order to reduce the overall cardiovascular risk in transplant patients lipid-lowering drugs, especially statins, have become widely used. However, the use of statins in transplant recipients taking cyclosporine A (CsA) results in significantly increased risk for statin induced side-effects such as myopathy and also rhabdomyolysis. Statin plasma concentrations are also increased several-fold and may be responsible for this increased risk. The other calcineurin inhibitor, tacrolimus (Tac), does not present such an effect on statin plasma concentrations during ordinary clinical use. AIM AND METHOD: The present study elucidated the in vitro cellular aspects and the mechanism of the pharmacokinetic interaction between atorvastatin (HMg-CoA reductase inhibitor) and the two calcineurin inhibitors, CsA and Tac. The inhibitory effect of CsA and Tac on cellular uptake of atorvastatin via the organic anion transporter polypeptide 1B1 (OATP1B1) was investigated in an in vitro over expression whole cell model. RESULTS: Atorvastatin was shown to be transported via the OATP1B1 transporter since cellular uptake was higher in OATP1B1 transfected HEK293 cells compared to mock cells. Inhibition of cellular uptake of atorvastatin was observed with CsA in OATP1B1 transfected cells. No clear inhibition of cellular uptake of atorvastatin was however observed for Tac in the OATP1B1 model, at least not in the lower concentration range investigated. CONCLUSION: The present in vitro study indicates that the cellular uptake of atorvastatin is mediated by OATP1B1 transporters and that CsA inhibits this drug transport. Tac on the other hand did not interfere with cellular uptake of atorvastatin, at least not in the concentration range investigated in this thesis. The observed interaction between atorvastatin and CsA is in line with findings in previous clinical studies, however further investigations is necessary in order to further characterize these findings. URI: http://hdl.handle.net/10037/1597 File(s) in this item: 1
thesis.pdf (754.2Kb) -
Rist, Maria (Master thesis; Mastergradsoppgave, 07-Jun-2011)[+][-]
Abstract: The incidence rate of malignant melanoma is increasing in Norwegian population as well as worldwide. It’s one of the most aggressive human cancers showing exceptional abilities to metastasize and develop resistance to therapy, and ccurrently there are no effective treatments against metastatic melanoma. Traditionally, melanoma aggressiveness was linked to intrinsic properties of the malignant cells themselves. However, it is becoming apparent now that the tumour microenvironment (TME) factors – non-malignant (stroma) cells, soluble molecules and extracellular matrix components – can play an important role in modulating metastatic properties and drug-sensitivity of cancer cells. In the present work we investigated how various TME factors like extracellular matrix components like fibronectin and laminin and soluble factors released from mice organs – common sites of melanoma metastasis - affected melanoma cells, specifically their metastasis-associated properties like growth/proliferation and sensitivity to the experimental dug Elesclomol. The study was based on three-dimensional (3D) in vitro cultures, where melanoma cells were grown in a Collagen or Matrigel matrix in the presence of investigated factors of TME. Two melanoma cells lines, Melmet 1 and Melmet 5 derived from the metastatic melanoma patents with different clinical indications were employed. It was observed that fibronectin and laminin did not have a notable effect on cell growth or viability. However, the soluble factors from the organs showed a slight stimulating effect on cell growth and a notable effect on cell morphology and growth pattern. The latter was especially pronounced for the bone marrow-derived factors. Comparison of the sensitivity of Melmet cells to Elesclomol in 3D versus 2D revealed, that 3D cultures were less sensitive to the drug, and that Melmet 5 was less sensitive compared to Melmet 1. The sensitivity was not modulated by the soluble factors derived from the healthy or metastatic brain. URI: http://hdl.handle.net/10037/3405 File(s) in this item: 1
thesis.pdf (1.412Mb) -
En legemiddeløkonomisk analyse av acetylsalisylsyre som primærprofylakse mot hjerte- og karsykdommerEriksen, Heidi-Mirelle (Master thesis; Mastergradsoppgave, May-2009)[+][-]
Abstract: Verdens helseorganisasjon (WHO) anbefaler primærforebyggende behandling med acetylsalisylsyre (ASA) hos pasienter med forhøyet risiko for utvikling av hjerte- og karsykdom. Per i dag ytes det ikke generell refusjon til forebyggende behandling med lavdosert ASA. Det var behov for å kartlegge hvorvidt primærforebygging av kardiovaskulære sykdommer med ASA viste seg å være en god utnyttelse av samfunnets begrensede ressurser. Hensikten med oppgaven var å belyse hvorvidt Albyl-E® oppfylte de faglige kriteriene for refusjon ved primærforebygging av hjerte- og karsykdommer. For å belyse det fjerde faglige kriteriet i Legemiddelforskriftens § 14-13, ble det utført tre legemiddeløkonomiske analyser. Den overordnede konklusjonen fra denne oppgaven er at ASA er et refusjonsverdig behandlingsalternativ for primærforebyggende behandling av pasienter med forhøyet risiko for hjerte- og karsykdommer. URI: http://hdl.handle.net/10037/2214 File(s) in this item: 1
thesis.pdf (2.005Mb) -
Nguyen, Tri Chinh (Master thesis; Mastergradsoppgave, 20-May-2009)[+][-]
Abstract: Invasiv MRSA-infeksjon initieres på sykehus og behandles med vancomycin eller linezolid. Vancomycin mot annen infeksjon enn i tarmen kan bare tas som infusjon og administreres derfor vanligvis kun på sykehuset. Linezolid kan tas som infusjon eller tabletter. Så lenge behandlingen foregår på sykehuset dekker sykehuset kostnadene til begge legemidler. Både vancomycin og linezolid har refusjon gjennom blåreseptordningen hvis en pasient blir utskrevet og trenger legemidler mot sin MRSA-infeksjon. Å bli utskrevet før antibiotikakuren er helt ferdig er imidlertid mer aktuelt hvis pasienter bruker linezolid peroralt. Problemstillingen i denne masteroppgaven er hvorvidt det er kostnadseffektivt fra et samfunnsperspektiv å behandle med linezolid (delvis hjemme) i forhold til vancomycin-infusjon på sykehus ved en invasiv MRSA-infeksjon. Det vurderes også om kostnadsbildet sett bare fra sykehusperspektivet kan påvirke behandlingsvalg. Målsettingen er å bidra til et bedre grunnlag for å foreta disse vurderingene. Basert på litteraturgjennomgang legges det til grunn en antagelse om legemidlenes likeverdighet og at det er grunnlag for en kostnadminimerings-analyse (CMA). En klinisk studie av Li et al. beskriver ressursbruk i forbindelse med behandling av MRSA-infeksjoner med linezolid eller vancomycin. Det er utført en piggyback analyse av denne studien etter retningslinjer utarbeidet av Statens legemiddelverk. Forskjell i kostnad mellom behandlingsalternativene er beregnet på grunnlag av ressursforbruket beskrevet i studien til Li supplert med informasjon om ressursforbruk i Norge som beskrevet i MRSA-veilederen og kartlagt på Universitetssykehuset i Nord-Norge (UNN). Det er brukt norske enhetskostnader for beregning av utgiftene. Fra et samfunnsperspektiv er besparelsen per MRSA-infeksjon ved kompliserte hud- og bløtvevsinfeksjoner ved bruk av linezolid på 51 256 kr per tilfelle. For andre MRSA-infeksjoner påløper det en ekstra kostnad på 31 132 kr ved bruk av linezolid. Der linezolidbehandling er lønnsomt i et samfunnsperspektiv er det enda mer lønnsomt fra et sykehusperspektiv. Linezolid er et kostnadseffektivt alternativ til vancomycin ved behandling av invasiv MRSA-infeksjon når det brukes mot kompliserte hud- og bløtvevsinfeksjoner. Linezolid er imidlertid ikke kostnadseffektivt når MRSA-infeksjonen ikke er en komplisert hud- og bløtvevsinfeksjon. Nøyaktig form for infeksjon, faren for utvikling av uheldig resistens og øvrige usikkerhetsmomenter ved analysen bør vurderes før man tar et valg om man skal bruke linezolid eller vancomycin ved MRSA infeksjoner. URI: http://hdl.handle.net/10037/2201 File(s) in this item: 1
thesis.pdf (531.0Kb) -
Øren, Kari (Master thesis; Mastergradsoppgave, 16-Jun-2008)[+][-]
Abstract: Bakgrunn: Osteoporose er en systemisk skjelettsykdom med redusert beinmasse og endring i beinvevets mikroarkitektur, med økt risiko for brudd som følge. Den vanligste årsaken til sekundær osteoporose er peroral glukokortikoidbehandling og blant langtidsbrukere av glukokortikoider vil nærmere halvparten utvikle osteoporose og brudd. Glukokortikoider brukes ved en rekke autoimmune sykdommer, der sykdommen i seg selv ofte er disponerende faktor for osteoporose. Ved behandling med glukokortikoider er risiko for brudd til stede ved høyere BMD enn ved andre former for osteoporose. Behandling med legemidler som øker bentettheten bør derfor starte tidligere ved glukokortikoid-indusert osteoporose enn ved andre former for osteoporose. Statens legemiddelverk anbefaler oppstart med bisfosfonater til alle som skal behandles med perorale glukokortikoider og som har T-score ≤ -1, og/eller hvis flere risikofaktorer for utvikling av osteoporose ligger til grunn. Det ytes ikke generell refusjon for forebyggende behandling med bisfosfonater ved glukokortikoid-indusert osteoporose. Problemstilling: Hensikten med oppgaven er å utføre en kostnadseffektivitetsanalyse av bisfosfonatet risedronat ved forebygging og behandling av glukokortikoid-indusert osteoporose. Den inkrementelle kostnadseffektivitetsratioen, ICER, er beregnet ved sammenligning av risedronat og placebo ved glukokortikoid-indusert osteoporose. Det er utført en analyse for postmenopausale kvinner og en for menn. Analysen gir grunnlag for vurdering om hvorvidt forebygging og behandling av glukokortikoid-indusert osteoporose med risedronat kan være en god utnyttelse av samfunnets begrensede ressurser til helse. Materiale og metode: En meta-analyse av Wallach et al. har påvist signifikant forskjell i BMD og andel vertebrale kompresjonsbrudd ved bruk av risedronat sammenlignet med placebo for forebygging og behandling av glukokortikoid-indusert osteoporose. Det er utført en piggy-back analyse av meta-analysen av Wallach et al. etter retningslinjer utarbeidet av Statens legemiddelverk. ICER er beregnet for kostnader per unngåtte vertebrale kompresjonsbrudd. Norske retningslinjer for behandling av osteoporotiske brudd er brukt som grunnlag for ressursberegning ved symptomatiske vertebrale kompresjonsbrudd. Det er brukt norske enhetskostnader ved utregning av utgiftene for ressursbruket. Resultat: For postmenopausale kvinner er kostnad per unngåtte vertebrale kompresjonsbrudd 21 105 kroner. For menn er kostnader per unngåtte vertebrale kompresjonsbrudd 15 269 kroner. Sensitivitetsanalysene viser at de parameterne som har størst påvirkning på endring i ICER er kostnader og effekt av risedronat. Konklusjon : Det kan være rimelig å anse forebygging og behandling av glukokortikoid-indusert osteoporose med risedronat for kostnadseffektivt både for postmenopausale kvinner og for menn. URI: http://hdl.handle.net/10037/1591 File(s) in this item: 1
thesis.pdf (595.4Kb) -
Rakvaag, Hilde (Master thesis; Mastergradsoppgave, 19-Jun-2007)[+][-]
Abstract: Makrofager kan utgjøre en betydelig del av en kreftsvulst. Det er tidligere vist at monocytter ved differensiering mot makrofager uttrykker økte mengder av enkelte cysteinproteaser. Maligne celler er vist å bruke cysteinproteaser i forbindelse med metastasering, og endogene cysteinproteasehemmere antas å kunne hemme denne prosessen. Det var derfor interessant å studere reguleringen i uttrykk og aktivitet av cystatiner ved differensiering av monocyttiske celler mot makrofager. Det ble etablert en funksjonell metode for måling av inhibitorisk aktivitet mot cysteinproteaser i laboratoriet ved hjelp av fluorometrisk måling med cysteinproteasen papain som enzym. Metoden ble brukt til å måle inhibitorisk aktivitet av cystatiner i THP-1 celler (en human monocyttliknende akutt leukemisk cellelinje), i diverse humane kreftcellelinjer, i diverse xenografter (human/mus), og i cystatin M-transfekterte HEK 293 celler (nyreepitelceller). THP-1 celler ble stimulert med PMA (40 ng/ml) i 24 timer, og dyrket i opptil 10 dager. Ved stimulering med PMA gikk cellene fra å være frittlevende monocytter til å bli adherente makrofager. Grad av inhibitorisk aktivitet ble regnet ut i inhibitoriske enheter per mg totalprotein for cellelysater og inhibitoriske enheter per ml for cellemedier. En inhibitorisk enhet ble definert som den konsentrasjonen som må til for å hemme 50 % av papainaktiviteten. Uttrykk av cystatinene C, M og F ble analysert ved hjelp av immunodeteksjon (Western blotting). Det ble sett på endring av total inhibitorisk aktivitet over tid, og en eventuell sammenheng mellom inhibitorisk aktivitet og uttrykk av cystatin C, F og M. Målingene i medieprøver fra cystatin M-transfekterte celler viste tydelig økt inhibitorisk aktivitet i de transfekterte cellene, noe som bekreftet at metoden fungerte for å måle hemming forårsaket av ekstracellulært cystatin M. Det ble observert en tidsavhengig økning i inhibitorisk aktivitet både i cellelysater og cellemedier. Uttrykk av cystatin C og M ble detektert, men ikke cystatin F. Det ble observert en sammenheng mellom den tidsavhengige økningen i ekstracellulær inhibitorisk aktivitet og uttrykk av ekstracellulært cystatin M. URI: http://hdl.handle.net/10037/1187 File(s) in this item: 1
thesis.pdf (443.1Kb) -
Dyrhaug, Sara Ann (Master thesis; Mastergradsoppgave, 20-May-2011)[+][-]
Abstract: Abstract Background– All solid organ transplanted patients are treated with immuno suppression medications to keep the immune system from rejecting the transplanted organ. Unfortunately the suppressed immune system makes the body more exposed for cancer and opportunistic infections. Among the most important viruses that causes one of these opportunistic infections is cytomegalovirus (CMV). A local project showed that not all transplanted patients on CMV prophylaxis get the right dose according to creatinine clearance (CrCl), and that the patients who had not been prescribed the recommended dose according to CrCl had a higher incident of CMV disease than those adjusted as recommended. The Quality improvement team for the transplant unit therefore suggested that a project could further investigate these issues. Aim and objectives – The aim of this project was to critically review and evaluate the processes in the prescribing and administration of valganciclovir for cytomegalovirus prophylaxis in liver, kidney or pancreas transplantation. Methods – Semi-structured one-to-one interviews with 2 nurses and 6 prescribers were conducted to establish current practice in prescribing, administration and monitoring of valganciclovir. A review of the local protocols at the transplant unit was conducted. To assess the harm a database analysis on the incident reporting system and a retrospective review of clinical records of 4 patients was undertaken. A questionnaire was developed for staff to self-assess the risk of harm of the whole process of CMV prophylaxis treatment. Pharmaceutical care issues relevant to CMV prophylaxis were recorded prospectively by clinical pharmacists over a two month period. Results – The semi-structured interviews with prescribers indicated that: 1) Prescribers often fail to recognise that the valganciclovir dose should be adjusted with changing CrCl. 2) That the laboratory test results taken at the clinic do not come back until the evening and are therefore not available at the time of prescribing, 3) There are gaps of knowledge, especially in the junior doctors. Reviews of local protocols suggested a need for update of the protocols and inclusion of detailed dosing guidance. The one incident reported in the database in terms of valganciclovir involved a missed dose. Case note reviews of four patients identified that dose adjustments are appropriate in 2 cases, 1 case was borderline and the other was a complex case but was judged to be appropriate. The questionnaire identified that there was agreement among healthcare professionals that there is a risk of errors that might lead to harm associated with all stages of valganciclovir use. Two clinical pharmacists recommended adjustment of valganciclovir 12 times in 7 patients in a time period of approximately two months. Conclusion – the outcomes from the interviews and pharmaceutical care issues analysis confirm the previous observation that the dose of valganciclovir is not always adjusted according to CrCl. Recommendations for improvement are to ensure modified guidelines are implemented to ensure all prescribers are aware of need for dose adjustment. Further work can be undertaken to measure the benefit after implement of the recommendations to assess improvement. URI: http://hdl.handle.net/10037/3420 File(s) in this item: 1
thesis.pdf (2.545Mb) -
Majid Alwan, Ahmed (Master thesis; Mastergradsoppgave, 11-Jun-2012)[+][-]
Abstract: Cardiovascular disease is strongly associated with diabetes; hypertension is prominent in diabetic patients. In 2003 a pharmacist-led cardiovascular risk reduction clinic was established to reduce cardiovascular risk in diabetic patients. The aim of this study was to evaluate the feasibility of outcome measures to inform a future prospective study to evaluate the pharmacist-led clinic and to measure the impact of the clinic on cardiovascular risk reduction. A spreadsheet was designed to be populated with patients’ information from patients attending the pharmacist-led clinic and the usual care. The process of data collection was performed retrospectively by case note review. Forty five patients were included in the intervention group (pharmacist's patients) and 42 in the control group (doctor's patients). There were significant differences in duration of diabetes (p=0.003), HbA1c (p=0.026) and number of comorbidities (p0.022) at baseline. The reduction in SBP was significant (p=0.0088) and the number of patients reaching target BP was significant (p =0.0036). Reduction in DBP, ACR and total cholesterol was insignificant. There was a significant difference in the number of antihypertensives started or increased (p<0.001) and a significant difference in the number of medication related problems actioned (p=0.0058). Reduction in BP and the proportion of patients reaching target BP change in pharmaceutical care plan drug therapy problems actioned can be used as outcome measures and primary end point in the future study. Reduction in ACR and the number of hospital admission might be used as feasible outcome measures if the intervention and the control group in the future study are similar and randomised correctly. URI: http://hdl.handle.net/10037/4322 File(s) in this item: 1
thesis.pdf (5.689Mb) -
Kvalvågnæs, Kristine (Master thesis; Mastergradsoppgave, 20-May-2008)[+][-]
Abstract: In Drug Discovery the first pharmacokinetic in vivo study of new compounds is of great importance to provide an initial assessment of the drug pharmacokinetik (PK) parameters. Data from these studies is used to optimize the PK properties of the chemical series and to calculate the initial doses in further in vivo studies. Because of the everexisting demand to increase throughput in Drug Discovery, there is a constant need for improved methods that provide faster bioanalysis or a reduced amount of samples. The aim of this study was to develop a method for sample pooling of three standardized pharmacokinetic in vivo studies. Strategies for sample reduction, fast chromatography, sensitivity and avoiding ionization suppression was investigated. In this study six reference compounds were selected to examine how sample pooling influences accuracy, precision, LOQ and PK-parameters. Sample preparation was performed by protein precipitation followed by HPLC-MS/MS and UPLC-MS/MS analysis. Diazepam, propranolol and imipramine were analysed in positive ESI mode whilst naproxen, diclophenac and rofecoxib were analysed in negative ESI mode. As warfarin can be detected both modes it was used as internal standard for all compounds. Spiked plasma (simulated to PK profiles) and samples from in vivo studies was used for the assessment. Equal volumes of three plasma samples corresponding to each time point of three individually dosed rats were pooled. The matrix effect of different formulations, e.g. cyclodextrine in terms of ionization suppression was examined. URI: http://hdl.handle.net/10037/1584 File(s) in this item: 1
thesis.pdf (996.3Kb) -
Fazelpour, Maryam (Master thesis; Mastergradsoppgave, 06-Jun-2008)[+][-]
Abstract: Natural transformation is recognaized as a major horizontal gene transfer mecahnism which impacts the genetic adaptaion , diversity and evolution of prokaryotes. Natural ransformation is uptake of extracellular DNA and its integration in a host genome. The fact that species take up foregin nucleotide sequences is believed to be followed by elimination of non-adventageous DNA sequence since bacterial genome do not grow in size.Transfer of gene from one species into the gene pool of another by backcrossing of hybid transformants with one parents is defined as intrgression. In this study the hypothesis that bacteria during introgrssion might regulate aquisition of foreign DNA by non-selected sequence by recombination was examined. The thesis contribute to earlier (Ray 2007)and ongoing projects investigating the fate of non-selected DNA during introgression of a choromsomal antibiotic resistance gene (nptII) in the bacterium A. baylyi. Hybrid transormants f A.baylyi ADP17021 contained a kanamycin resistance gene ande a mutS-gene deletion and an undeteramined amount of the donor strain A.sp.62A1. In this study DNA sequencing technologies and the Acinetobacter baylyi BD413 (ADP1) published geneome sequence was used to achive important results as identifying putative recombination junctions in ten back-transformants among the 10th and first generation and the effect of methyl-directet mismatch repair (mutS-deletion) on flanking DNA aquired by the recipient. The generation of the initial heterogamic transformation and ten subsequent backcross transformants were performed in a previous study (Ray, 2007). The aim of this study was identifying recombination junctins and the insert size of flanking DNA. It was clear that back-cross transformants harboured a significantly shorter donor sequence when compared to the initial genration. This indicates that during introgression, the non selected sequence will be gradually eliminated. URI: http://hdl.handle.net/10037/1569 File(s) in this item: 1
thesis.pdf (1.524Mb) -
Rud, Ane Kristine Kongsgaard; Lund-Iversen, Marius; Berge, Gisle; Brustugun, Odd Terje; Solberg, Steinar; Mælandsmo, Gunhild; Pedersen, Kjetil Boye (Journal article; Tidsskriftartikkel; Peer reviewed, 2012)[+][-]
Abstract: The metastasis-promoting protein S100A4 induces expression of ephrin-A1 and osteopontin in osteosarcoma cell lines. The aim of this study was to investigate S100A4-mediated stimulation of ephrin-A1 and osteopontin in non-small cell lung cancer (NSCLC) cell lines, and to characterize the expression of these biomarkers in primary tumor tissue from NSCLC patients. Four NSCLC cell lines were treated with extracellular S100A4, and ephrin-A1 and osteopontin expression was analyzed by real time RT-PCR and Western blotting. Immunohistochemical staining for S100A4, ephrin-A1 and osteopontin was performed on tissue microarrays containing primary tumor samples from a cohort of 217 prospectively recruited NSCLC patients, and associations with clinicopathological parameters were investigated. S100A4 induced ephrin-A1 mRNA and protein expression in adenocarcinoma, but not in squamous carcinoma cell lines, whereas the level of osteopontin was unaffected by S100A4 treatment. In primary tumors, moderate or strong immunoreactivity was observed in 57% of cases for cytoplasmic S100A4, 46% for nuclear S100A4, 86% for ephrin-A1 and 77% for osteopontin. Interestingly, S100A4 expression was associated with ephrin-A1 also in vivo, but there was no association between S100A4 and osteopontin. Expression levels of S100A4 and ephrin-A1 were significantly higher in adenocarcinomas compared to other histological subtypes, and S100A4-positive tumors were smaller and more differentiated than tumors without expression. Our findings suggest that S100A4, ephrin-A1 and osteopontin are involved in the biology of NSCLC, and further investigation of their potential use as biomarkers in NSCLC is warranted. URI: http://hdl.handle.net/10037/4903 File(s) in this item: 1
article.pdf (721.6Kb) -
Mahmoud, Herem Fatih (Master thesis; Mastergradsoppgave, 21-Jun-2010)[+][-]
Abstract: This thesis is part of a randomized controlled trial at the University Hospital of Northern Norway (UNN). The aim of the thesis was to get a deeper understanding of how patients experience pharmaceutical follow-up and to examine the factors that the patient perspective is of importance in the follow-up. This study included 4 patients with cardiovascular disease, and was based on qualitative research methods to understand the patient’s experiences with the follow-up through a depth interview. A hermeneutic approach was used in the analysis and interpretation of the interview. The results of this study were presented in the form of empiricism close headlines which was then discussed. Interpretation of the informants stories are held up toward previous research and theoretical perspectives like empowerment and paternalism. The informants were positive toward pharmaceutical follow-up and believed they had learned both about their drugs and their diseases. This has given the patients a feeling of safety in everyday life. Another important factor that emerged in this work was the importance that the pharmacist spending enough time in conversation with the patient. Patients wanted more time with the general practitioner (GP) doctor, but also expressed that through collaboration between pharmacist and GP the need for medical information could be reduced. Informants also mentioned that it is important for the pharmacist to highlight their role both in a pharmacy and other places, such as in hospital wards. This thesis has discussed experiences with pharmaceutical follow-up of informants with heart disease. It can help to provide a practical basis for the establishment of pharmaceutical follow-up. URI: http://hdl.handle.net/10037/2754 File(s) in this item: 1
thesis.pdf (444.7Kb) -
Vu, Kim Anh Thi (Master thesis; Mastergradsoppgave, Jun-2012)[+][-]
Abstract: Krill er rik på omega-3 fettsyrene EPA og DHA, noe som forklarer den store kommersielle interesse for fangst og foredling av krill. I krillolje er det mye fosfolipider sammenliknet med fiskeoljer. Flere hevder at EPA og DHA utnyttes bedre når de er bundet i fosfolipider enn når de fins i triacylglyserol (Bunea et al, 2004; Werner, Havinga et al, 2004). Det er gjort lite forskning på krillolje og helse. Studier som har blitt gjort av krillolje sammenlikner helseeffekten av krillolje med fiskeolje. En studie viste at krillolje reduserte kolesterol (LDL) og økte nivået av det gode kolesterolet (HDL). I tillegg hjelper det å kontrollere blodsukkernivået og kan dermed bidra til å forebygge diabetes (Bunea et al, 2004). I en dobbeltblind klinisk studie reduserte krillolje inflammasjon og artritt symptomer i en kort behandlingsperiode på 7 og 14 dager (Deutsch, 2007; Massrieh, 2008). En annen studie viste at kvinner med premenstruelt syndrom (PMS) ble mindre plaget (Sampalis et al, 2003). Målet med oppgaven var å analysere innholdet av fettklasser og fettsyresammensetning av kommersielle krilloljeprodukter. Fire forskjellige krilloljeprodukter ble undersøkt. Fettklassene ble separert ved bruk av fast fase ekstraksjon og analysert ved tillaging av fettsyremetylestere for videre analyse med gasskromatografi. Fettsyrene fra Complete krillolje og utvalgte fraksjoner etter fast fase ekstraksjon ble identifisert ved å sammenlikne observerte retensjonstider med kjente fettsyrestandarder. Analyse fra fettsyresammensetningen av Complete krillolje viste at innholdet av EPA var 16,7 % og 8,8 % DHA. Blant mettede fettsyrer var 16:0 den dominerende fettsyren og 18:1, 20:5n-3 og 22:5n-6 blant umettede og flerumettede fettsyrer. Fosfolipider, triacylglyseroler og frie fettsyrer var de viktigste fettklassene i krillolje. Ulike lipidklasser bestod av relativt forskjellige fettsyrer. EPA utgjorde 31,5 % og DHA 15 % i fraksjonen som inneholdt fosfolipider. Tilsvarende 24,6 % EPA og 16 % DHA i frie fettsyre fraksjonen. Fosfolipider og frie fettsyrer fraksjonene inneholdt mest flerumettede fettsyrer, mens den nøytrale lipidfraksjonen inneholdt mest mettede fettsyrer og lite flerumettede fettsyrer. Et av krilloljeproduktene hadde en relativt høy andel frie fettsyrer som er over den anbefalte grenseverdien for marine oljer til humant konsum i følge Global Organization for EPA and DHA (GOEDs), mens de tre andre krilloljeproduktene ligger innenfor den anbefalte grenseverdien. URI: http://hdl.handle.net/10037/4326 File(s) in this item: 1
thesis.pdf (1.660Mb) -
Jensen, Anna (Master thesis; Mastergradsoppgave, 20-May-2010)[+][-]
Abstract: Masteroppgaven har som mål å kartlegge kunnskap om kolesterolsenkende behandling (statiner)blant kundene på apotek. Oppgaven er gjennomført på tre sykehusapotek: i Tromsø, Bodø og Trondheim. URI: http://hdl.handle.net/10037/2749 File(s) in this item: 1
thesis.pdf (609.8Kb) -
Gravem, Hilde (Master thesis; Mastergradsoppgave, 16-Jun-2006)[+][-]
Abstract: Gemcitabine, an anticancer agent, is currently in clinical use for the treatment of several types of cancer. Unfortunately, gemcitabine is rapidly metabolised with a short plasma half-life and its cytostatic action is strongly exposure-time dependent. In order to achieve the required concentration over sufficient periods of time, repeated application of relatively high doses is required. This, in turn, leads to dose-limiting systemic toxicity. In order to improve both the efficiency and the toxicity profile of gemcitabine the use of liposomes appears promising. In literature, only a few attempts to entrap gemcitabine within liposomes are found, however none of these liposomal formulations has reached clinical practice. In this study, an ammonium sulphate gradient was tried for active loading of gemcitabine into liposomes. Firstly, unsaturated egg phosphatidyl choline liposome dispersion was prepared with ammonium sulphate as hydration medium by the hand shaken method followed by filter extrusions with decreasing filter sizes down to 0.1 µm. Then, a transmembrane ammonium sulphate gradient was generated by removing extra-liposomal ammonium sulphate by size exclusion chromatography. Quantitative determination of the ammonium sulphate concentration, both outside and inside the liposomes, via electric conductivity measurement revealed that a gradient of external to internal ammonium sulphate of about 1:58 was achieved. Secondly, the liposomes were loaded with gemcitabine by incubation at different conditions. Among the loading conditions tested, a total loading time of 24 hours including heating for 2 hours at 60 ˚C seemed advantageous in achieving efficient loading. A higher starting concentration of gemcitabine resulted in enhanced loading efficiency, calculated on a molar basis. Comparing these results to a VPG passive loading technique, the active loading technique resulted in a gemcitabine:lipid ratio of about 1:20 versus 1:140 for the vesicular phospholipid gel loaded liposomes. Unfortunately, the actively loaded liposomes revealed poor storage stability with 80 % leakage after 24 hours. Further studies are needed in order to optimise loading and stability of the liposomes. URI: http://hdl.handle.net/10037/22 File(s) in this item: 1
thesis.pdf (714.0Kb) -
Bruvoll, Tina Mari (Master thesis; Mastergradsoppgave, 20-May-2008)[+][-]
Abstract: Bakgrunn: Antibiotikaresistens er i dag blitt et signifikant problem på grunn av vårt misbruk – både overforbruk, underforbruk, feilbruk, manglende compliance, inadekvat dosering og ikke minst en likegyldighet til bruk. For alvorlige infeksjonssykdommer som sepsis kan dette gi dramatiske konsekvenser, da man er avhengig av effektive terapimidler da sykdommen er forbundet med høy morbiditet og mortalitet. Selv om Norge enda er et av de landene hvor resistensproblemet er minst så er det viktig at det tas på alvor, og at terapi følger gitte retningslinjer - blant annet ved sepsis hvor en initial bredspektret empirisk terapi raskest mulig bør endres til mer smalspektret terapi for å redusere risikoen for resistensutvikling. Formål: Formålet med denne studien var å undersøke om diagnostisk informasjon i form av mikrobiologisk bakterieidentifikasjon og resistensbestemmelse førte til endringer av bredspektret empirisk terapi ved bakteriemi. Karakterisering av endringer gjort og behandlingsregimer, og vurdere disse i forhold til gitte retningslinjer utarbeidet ved UNN i 2005 var også et mål med studien. Studien ble utført ved Avdeling for Mikrobiologi og Smittevern ved UNN, og sammenlignet med tilsvarende studie utført ved UNN i 2005 og ved St. Olavs Hospital i 2003. Metode: Studien er en deskriptiv observasjonsstudie basert på retrospektive data. Studiepopulasjonen var pasienter innlagt på UNN og med positive blodkulturer i 2006. Pasientjournaler og mikrobiologiske arbeidsskjemaer ble gjennomgått, og det ble registrert antibiotikabehandling og mikrobiologiske besvarelser for gitte registreringsperioder. Resultater: Av 276 episoder med reell bakteriemi ble det registrert endringer i terapiregimene i 34,1 % av besvarte episoder etter mikroskopifunn, 36,2 % etter preliminær resistensbestemmelse og 12,0 % etter definitiv resistensbestemmelse. Ved mistenkt bakteriemi var monoterapi med cefalosporiner eller kombinasjonsterapi med penicilliner og aminoglykosider mest fremtredende. Etter at mikrobiologiske data forelå bestod behandlingen av episoder med gram negative bakterier i hovedsak av monoterapi med cefalosporiner eller kombinasjonsterapi med enten penicilliner og aminoglykosider eller cefalosporiner og aminoglykosider. Behandlingen av episoder med gram positive bakterier bestod i hovedsak av monoterapi med penicilliner eller kombinasjonsterapi med penicilliner og aminoglykosider. Konklusjon: Resultatene tyder på at mikrobiologiske data hadde innvirkning på valg av antibiotikaregime ved bakteriemi. Det ble benyttet empirisk terapi anbefalt i antibiotikaveilederen i større grad ved UNN i 2006 enn ved UNN i 2002 og St. Olavs Hospital i 2002. Andelen monoterapi økte ved UNN fra 2002 til 2006. Resultatene av studien gir inntrykk av at terapien endret seg i henhold til bakterieidentifikasjon og resistensbestemmelse. URI: http://hdl.handle.net/10037/1583 File(s) in this item: 1
thesis.pdf (1.080Mb) -
Engesland, André (Master thesis; Mastergradsoppgave, 20-May-2010)[+][-]
Abstract: Hydrogels made of chitosan has a well-established place in drug delivery for the skin. Our particular interest were hydrogels for wound healing. Hydrogels from low, medium and high molecular weight were prepared in different concentrations for texture and release characterization incorporating liposomes and chloramphenicol as a model drug. A method for comparing viscosity between gels was established with a Texture analyser and back-extrusion method. The method proved to be able to distinguish differences between gels with standard deviations varying with less than 2%. Different liposomal chitosan hydrogels were prepared with or release studies with the model drug chloramphenicol. The release study proved that liposomal hydrogels could act as vehicles for antibiotics in depot formulations. Chitosan preparations were also tested under both accelerated stability testing and freeze-thaw test. Stability was improved with glycerine in the hydrogels. Stability seemed to be dependant on molecular weight and concentration of chitosan. The low molecular weight chitosan gels were the least stable, and higher concentrations can give more stable gels. URI: http://hdl.handle.net/10037/2750 File(s) in this item: 1
thesis.pdf (2.452Mb) -
Identifisering av en gruppe glykosyltransferaser som mulige målgener for transkripsjonsfaktoren Pax6Nguyen, Huong-Lan Thi (Master thesis; Mastergradsoppgave, 09-Nov-2009)[+][-]
Abstract: Det har vært stadig mer forskning på rollen av glykosylering i utvikling av sykdommer i de siste tiårene. Glykosylering av proteiner er en prosess hvor karbohydrat grupper overføres til et protein ved hjelp av glykosyltransferaser. Denne prosessen er nødvendig for riktig folding av proteiner som gir riktig funksjon til ulike proteiner. Endringer i glykosylering av proteiner har vist å ha sammenheng med utvikling av en rekke sykdommer og kreft. Disse endringer i glykosylering kan oppstå som følge av endringer i uttrykksnivåer av glycosyltransferasene. Denne masteroppgaven har til hensikt å verifisere om en gruppe glykosyltransferaser (Fut8, Mgat3, Ugt1a7c, St3gal6, St6gal1, Gcnt1 og Gcnt2) er mulige målgener for transkripsjonsfaktoren Pax6. Metodene RT-PCR og qPCR ble brukt for å se på uttrykket og eventuelle nedreguleringer av de sju testede glykosyltransferaser i FlpIn-3T3-Pax6 og FlpIn-3T3-Pax6(5a) på RNA-nivå. Det ble også brukt metoder som isolering av glykoproteiner ved hjelp av concavalin A (Con A) og Wheat Germ Agglutinin (WGA), immunopresipitering (IP), Western blot (WB) og immunohistokjemi (IHC) for å prøve og detektere endringer i glykosylering på protein-nivå. Resultat av denne masteroppgaven viste at de sju testede glykosyltransferasene blir nedregulert i nærvær av Pax6 og isoformen Pax6(5a) på RNA-nivå. Når det gjelder metodene glykoprotein isolering vha ConA og WGA og IP ble det ingen klare resultater, mens Western blot resultatet viste at nucleolin blir nedregulert både i Pax6 og Pax6(5a) på protein nivå. Konklusjonen for denne masteroppgaven er at vi har identifisert glykosyltransferasene Fut8, Mgat3, Ugt1a7c, St3gal6, St6gal1, Gcnt1 og Gcnt2 som nye målgener for Pax6. Disse glykosyltransferasene blir nedregulert i nærvær av Pax6 og Pax6(5a) og basert på tidligere funn har det vist at nedregulering av disse glykosyltransferasene fører til en rekke sykdommer. Resultatet vi ser i denne masteroppgaven har gitt en ytterligere innsikt i mulige rollen av Pax6 i regulering av de sju testede glykosyltransferasene i utvikling av sykdommer og kreft. URI: http://hdl.handle.net/10037/4399 File(s) in this item: 1
thesis.pdf (1.660Mb)
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