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Basnet, Purusotam; Skalko-Basnet, Natasa (Journal article; Tidsskriftartikkel; Peer reviewed, 2011)[+][-]
Abstract: Oxidative damage and inflammation have been pointed out in preclinical studies as the root cause of cancer and other chronic diseases such as diabetes, hypertension, Alzheimer’s disease, etc. Epidemiological and clinical studies have suggested that cancer could be prevented or significantly reduced by treatment with anti-oxidant and anti-inflammatory drugs, therefore, curcumin, a principal component of turmeric (a curry spice) showing strong anti-oxidant and anti-inflammatory activities, might be a potential candidate for the prevention and/or treatment of cancer and other chronic diseases. However, curcumin, a highly pleiotropic molecule with an excellent safety profile targeting multiple diseases with strong evidence on the molecular level, could not achieve its optimum therapeutic outcome in past clinical trials, largely due to its low solubility and poor bioavailability. Curcumin can be developed as a therapeutic drug through improvement in formulation properties or delivery systems, enabling its enhanced absorption and cellular uptake. This review mainly focuses on the anti-inflammatory potential of curcumin and recent developments in dosage form and nanoparticulate delivery systems with the possibilities of therapeutic application of curcumin for the prevention and/or treatment of cancer. URI: http://hdl.handle.net/10037/3877 File(s) in this item: 1
article.pdf (354.5Kb) -
Baumann, Markus (Master thesis; Mastergradsoppgave, Jun-2012)[+][-]
Abstract: Hookworms are parasitic nematodes that reside in the intestines of their host, where they feed on host blood. The large number of infected individuals and the long survival time inside the host makes it interesting to study the immunomodulatory activities of the hookworms. The excretory/secretory (ES) products are suspected to be responsible for these effects. One aim of this project was to fractionate the low molecular weight part (< 10 kDa) of ES products from the dog hookworm Ancylostoma caninum and test their activity in a mouse colitis model that resembles human Crohn’s disease. The results were inconclusive, but trends could be seen and it seems that two fractions might show activity in the future if the tests are scaled up. The second aim was to use Fmoc-SPPS to synthesise two disulfide-rich peptides that were identified in the transcriptome of hookworms. These peptides possess the cysteine framework of the sea anemone toxin ShK, which is able to block voltage-gated potassium channels. One peptide, Name2, was synthesised successfully and as predicted folded into a ShK-like domain as confirmed by NMR spectroscopy. The three dimensional structure of the peptide was determined and it was revealed to contain two helical segments that were braced by the three disulfide bonds. Difficulties were encountered in the synthesis of Acan1 and the correct peptide was not obtained. URI: http://hdl.handle.net/10037/4321 File(s) in this item: 1
thesis.pdf (17.23Mb) -
Berg, Camilla Torset (Mastergradsoppgave; Master thesis, May-2009)[+][-]
Abstract: Introduction The Edinburgh IMPACT (Improved Anticipatory Care and Treatment) is aimed at people with long term conditions, and focuses on improving patients’ quality of life and reducing preventable hospital admissions. The service is nurse led, and recently primary care pharmacists have been added to the team to perform a medication review pilot. Patients would be referred to the pharmacist, who would go to their house and review their medicines. The aim for this project was to assess pharmaceutical care needs of patients with heart failure, design a clinical document for the use in the care of these patients, and to develop a questionnaire to evaluate the medication review service. Methods A model of pharmaceutical care was adapted from a previous project, and was modified in order to show the multidisciplinary care for patients with heart failure. A pharmaceutical care plan for heart failure was developed by using a pharmaceutical care plan from previous work done on diabetes. A patient questionnaire with closed-ended questions was designed in order to evaluate the existing anticipatory care service. The draft care plan was revised following feedback from pharmacists in NHS Lothian. The draft patient questionnaire was piloted in two patients that had been seen by the pharmacist. Results The output from the project was a tool kit for documentation of the anticipatory care service to heart failure patients. The toolkit comprises; a model of care for heart failure, a two page clinical document (patient profile and care plan) that can be used in the care of patients with heart failure, and a patient questionnaire that enables other to evaluate the anticipatory care service when it is up and running properly. Conclusion The researcher has developed a set of tools that after some redesign and modifications can be used to support the care of patients with heart failure, and to evaluate the medication review service. URI: http://hdl.handle.net/10037/2179 File(s) in this item: 1
thesis.pdf (1.377Mb) -
Berg, Ole Aleksander (Master thesis; Mastergradsoppgave, 20-May-2011)[+][-]
Abstract: Trauma to the skin in the form of severe wound, particularly burns, can facilitate colonization of potentially life threatening bacterial infections. To prevent infections of the wounded area, antimicrobial agents are recommended as standard treatment. Topical administration of antimicrobial agents, such as mupirocin, can provide local therapy, while avoiding the risks of systemic administration. Mupirocin-in-liposomes-in hydrogels were proposed as advanced delivery system for this purpose. Up to now, no liposomal mupirocin for topical administration has been reported. Chitosan was selected as hydrogel matrix due to its biodegradability and in-built antimicrobial and wound healing potentials. Phosphatidylcholine liposomes containing mupirocin, namely non-sonicated and sonicated liposomes, were characterized for vesicle size and size distributions. Non-sonicated vesicles entrapped in average 74 and sonicated 49 % of mupirocin calcium, respectively. Sonication reduced the original vesicle size from around 1 micron down to 135 nm. Liposomes (10 %, w/w) were incorporated in chitosan hydrogels and liposomal hydrogels evaluated for their textural properties. Hydrogels were found to exhibit satisfactory adhesiveness and cohesiveness, with corresponding stability profile. Microbiological assessment confirmed antibacterial properties of liposomally entrapped mupirocin incorporated in hydrogels. In vitro and ex vivo (on pig skin) drug release profiles of various formulations containing mupirocin were performed on Franz diffusion cells. Liposomal hydrogels were compared with marketed mupirocin product, Bactroban® cream. The release studies showed that liposomal size affects the release of the incorporated drug. Liposomal hydrogels were shown to provide sustained release of incorporated mupirocin. In conclusion, liposomal hydrogels developed for mupirocin offer the potential to increase retention time and provide sustained release of a drug, which are important parameters for improved treatment of wounds, including burns. URI: http://hdl.handle.net/10037/3689 File(s) in this item: 1
thesis.pdf (71.30Mb) -
Brenne, Ingvild Synnøve (Master thesis; Mastergradsoppgave, 20-May-2009)[+][-]
Abstract: Background Hereditary non-polyposis colorectal cancer(HNPCC) is an autosomal dominantly inherited predisposition to a variety of epithelial malignancies most notable colorectal and endometrial cancer. Unlike other genetic predispositions to colorectal cancer HNPCC does not present with a premalignant phenotype, which as such makes it difficult to predict when or if an affected person will present with disease. The genetic basis of HNPCC has been conclusively shown to be due to mutations in genes involved in DNA mismatch repair; hMLH1, hMSH2 hMSH6 and PMS2. Methods Several reports suggest that genetic modifiers of disease risk are capable of influencing the age of disease onset in HNPCC and it is likely that many of them have not yet been identified. Recently several genome-wide association studies have revealed a number of colorectal cancer susceptibility loci on chromosomes 10p14, 8q23.3, 8q24, 11q23 and 18q21. These loci are of particular importance as they are associated with an increased risk of colorectal cancer and may therefore act as modifiers of disease risk in individuals diagnosed with HNPCC. Materials and methods 373 Australian and 311 Polish HNPCC patients with a molecular diagnosis of HNPCC have been examined for nine polymorphisms in the five loci described above. All DNA samples were genotyped to determine the allele frequency in the nine polymorphisms investigated. A statistically evaluation of the exact nature of the effect on disease risk was assessed using the statistical software package SPSS Graduate Pack Version 12.0. Results In this study, hMLH1 mutation carriers harbouring the variant genotype for polymorphism rs3802842 were associated to development of colorectal cancer (CRC) at an earlier age than hMLH1 carriers harbouring the heterozygous or wild type genotype. This suggests that the particular polymorphism might act as a modifier for disease development in hMLH1 mutation carriers. URI: http://hdl.handle.net/10037/2206 File(s) in this item: 1
thesis.pdf (954.2Kb) -
Glad, Trine; Brusetti, Lorenzo; Aars, Jon; Bernhardsen, Pål; Nielsen, Kaare Magne; Andersen, Magnus; Sundset, Monica Alterskjær (Journal article; Tidsskriftartikkel; Peer reviewed, 2010)[+][-]
Abstract: Background Polar bears (Ursus maritimus) are major predators in the Arctic marine ecosystem, feeding mainly on seals, and living closely associated with sea ice. Little is known of their gut microbial ecology and the main purpose of this study was to investigate the microbial diversity in faeces of polar bears in Svalbard, Norway (74-81 degrees N, 10-33 degrees E). In addition the level of blaTEM alleles, encoding ampicillin resistance (ampr) were determined. In total, ten samples were collected from ten individual bears, rectum swabs from five individuals in 2004 and faeces samples from five individuals in 2006. Results A 16S rRNA gene clone library was constructed, and all sequences obtained from 161 clones showed affiliation with the phylum Firmicutes, with 160 sequences identified as Clostridiales and one sequence identified as unclassified Firmicutes. The majority of the sequences (70%) were affiliated with the genus Clostridium. Aerobic heterotrophic cell counts on chocolate agar ranged between 5.0 x 104 to 1.6 x 106 colony forming units (cfu)/ml for the rectum swabs and 4.0 x 103 to 1.0 x 105 cfu/g for the faeces samples. The proportion of ampr bacteria ranged from 0% to 44%. All of 144 randomly selected ampr isolates tested positive for enzymatic beta-lactamase activity. Three % of the ampr isolates from the rectal samples yielded positive results when screened for the presence of blaTEM genes by PCR. BlaTEM alleles were also detected by PCR in two out of three total faecal DNA samples from faeces three polar bears. Conclusion The bacterial diversity in faeces from polar bears in their natural environment in Svalbard is low compared to other animal species, with all obtained clones affiliating to Firmicutes. Furthermore, only low levels of blaTEM alleles were detected in contrast to their increasing prevalence in some clinical and commensal bacterial populations. URI: http://hdl.handle.net/10037/3067 File(s) in this item: 1
article.pdf (594.6Kb) -
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) -
Carstens, Bodil Børte (Mastergradsoppgave; Master thesis, 20-May-2009)[+][-]
Abstract: Iron homeostasis is regulated by the interaction between the hormone hepcidin and the iron exporter ferroportin. Hepcidin is a cysteine-rich peptide which is secreted by hepatocytes in response to inflammation, eryhropoietic demand and iron stores. Hepcidin binds to its receptor ferroportin, inducing its internalisation and degradation, thus regulating the export of iron from cells to plasma. One of the aims of this study was to determine the three-dimensional (3D) structure of hepcidin using nuclear magnetic resonance (NMR) spectroscopy. The structure calculated consisted of a β-sheet with a hairpin loop showing a flexible N-terminus. The overall aim of this study was to analyse the interaction between hepcidin and ferroportin. Recently, mutational analysis revealed that hepcidin binds to a 20 residue extracellular loop on ferroportin, called the hepcidin-binding domain (HBD). Techniques including NMR spectroscopy, isothermal titration calorimetry (ITC), circular dichroism (CD) spectroscopy and surface plasmon resonance (SPR) spectroscopy were used. The results from all the assays performed indicate, however, that hepcidin does not bind to the HBD peptide. Three hepcidin analogues was synthesised to elucidate which residues in hepcidin that are important for the binding to ferroportin. The N-terminus of hepcidin is essential for binding to hepcidin and serial deletion of the N-terminal amino acids showed to cause progressive loss of activity when all five residues were deleted. Gly 20 was shown to have a key role in the interaction between hepcidin and ferroportin. This is the first mutation outside the N-terminus region that has activity. URI: http://hdl.handle.net/10037/2178 File(s) in this item: 1
thesis.pdf (1.391Mb) -
Christensen, Marit Bergheim (Master thesis; Mastergradsoppgave, May-2008)[+][-]
Abstract: Background Pharmaceutical care as a health care service has already made its mark and been shown to make an important contribution to the health care system. However, there is still a demand from the NHS among others, that pharmacist to a greater extent must document their provision of pharmaceutical care. Tested out in this project, is the application of a Care Issue Categorisation System. Aims To compare two clinical settings in terms of the profile of pharmaceutical care delivered and the profile of medication use. The findings will be reported in a way which allows quantitative comparison of pharmaceutical care issues addressed by the clinical pharmacy service in a proposed reporting, and a modified categorisation system will be use to accomplish this. Method A literature review were performed on pharmaceutical care, medicines management, common chronic diseases etc. Process maps were produced to describe the delivery of pharmaceutical care at the General Medical Ward at Glasgow Royal Infirmary. An existing categorisation system was modified and a guideline developed and both used for the analysis of documentation made by the pharmacists. Inter rater agreement on the categorisation system was tested and pharmaceutical activity was compared between two wards. Result The existing categorisation system was modified in several parts and tested by four investigators. Process maps and analysis of the care issues documented reveal that there was a inconsistency between the pharmacist’s provision of care and documentation. The comparison between two wards showed that the pharmacists had different priorities and documentation. Conclusion The modified categorisation system is tool that has the potential to aid future documentation of pharmaceutical provision of patient care. Comparison of pharmaceutical care activity between two ward showed that pharmacists are contribution to pharmaceutical care but that there are differences in their priorities and documentation of care issues URI: http://hdl.handle.net/10037/1573 File(s) in this item: 1
thesis.pdf (397.8Kb) -
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) -
Domingues, Sara; Harms, Klaus; Fricke, W. Florian; Johnsen, Pål Jarle; da Silva, Gabriela J.; Nielsen, Kåre M. (Journal article; Tidsskriftartikkel; Peer reviewed, 2012)[+][-]
Abstract: We have investigated to what extent natural transformation acting on free DNA substrates can facilitate transfer of mobile elements including transposons, integrons and/or gene cassettes between bacterial species. Naturally transformable cells of Acinetobacter baylyi were exposed to DNA from integron-carrying strains of the genera Acinetobacter, Citrobacter, Enterobacter, Escherichia, Pseudomonas, and Salmonella to determine the nature and frequency of transfer. Exposure to the various DNA sources resulted in acquisition of antibiotic resistance traits as well as entire integrons and transposons, over a 24 h exposure period. DNA incorporation was not solely dependent on integrase functions or the genetic relatedness between species. DNA sequence analyses revealed that several mechanisms facilitated stable integration in the recipient genome depending on the nature of the donor DNA; homologous or heterologous recombination and various types of transposition (Tn21-like and IS26-like). Both donor strains and transformed isolates were extensively characterized by antimicrobial susceptibility testing, integron- and cassette-specific PCRs, DNA sequencing, pulsed field gel electrophoreses (PFGE), Southern blot hybridizations, and by re-transformation assays. Two transformant strains were also genome-sequenced. Our data demonstrate that natural transformation facilitates interspecies transfer of genetic elements, suggesting that the transient presence of DNA in the cytoplasm may be sufficient for genomic integration to occur. Our study provides a plausible explanation for why sequence-conserved transposons, IS elements and integrons can be found disseminated among bacterial species. Moreover, natural transformation of integron harboring populations of competent bacteria revealed that interspecies exchange of gene cassettes can be highly efficient, and independent on genetic relatedness between donor and recipient. In conclusion, natural transformation provides a much broader capacity for horizontal acquisitions of genetic elements and hence, resistance traits from divergent species than previously assumed. URI: http://hdl.handle.net/10037/4919 File(s) in this item: 1
article.pdf (530.2Kb) -
Do, Minh-Anh Thuy (Master thesis; Mastergradsoppgave, 19-May-2012)[+][-]
Abstract: In the last decade, the investigation of marine natural products has resulted in a remarkable number of compounds with promising biological activities. Marine natural products have been shown to display antibacterial, antifungal, anticancer, antiviral, antiparasitic, anti-inflammatory activity and several other pharmacological activities of benefit to humankind. In this project, an investigation of the anti-inflammatory and immunostimulatory activities of extracts from two Arctic marine invertebrate species; a bryozoan, Eucratea loricata, and a sea urchin, Echinus esculentus, is presented. Anti-inflammatory activity was analyzed by using the monocyte/macrophage cell lines: THP-1 (accurate monocytic leukemia) and U937 (leukemic monocyte lymphoma). Immunostimulatory activity was analyzed by using THP-1 cell line. Effects on cell culture were monitored as reduced NFκB reporter activity in transfected cell line, and as reduced or increased production of the cytokines TNF-α and IL-1β. Bioassay-guided fractionation of the extracts revealed the presence of anti-inflammatory activity in the Echinus esculentus extracts. The structure of the target compound was partly elucidated using high resolution mass spectrometry, mass spectrometric fragmentation, and nuclear magnetic resonance spectroscopy. In addition, this present project provides background information about natural product research and current anti-inflammatory investigations of marine invertebrate species. URI: http://hdl.handle.net/10037/4323 File(s) in this item: 1
thesis.pdf (2.884Mb) -
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) -
Elvheim, Iselin Sørstad (Master thesis; Mastergradsoppgave, Jun-2011)[+][-]
Abstract: The relaxin family of peptides consists of seven structurally related peptides, with a wide variety of biological functions, ranging from involvement in reproductive processes to functions as neuroendocrine modulators. Because of the complex, two-chained structure of the relaxins, and their lack of specificity for the various relaxin family receptors (RXFPs), design of simpler, more selective analogues is important for further investigation of their biological functions and as potential drug leads. The aim of this project was to introduce a helical structure around the receptor-binding region of single-chain relaxin analogues. This was approached by utilising helix capping sequences on truncated relaxin B-chains and by grafting of residues important for binding onto a stable peptide scaffold. Helix capping enhanced the helical properties compared to previous single- chain analogues, but was unable to introduce a sufficiently stable helix. Despite the increased helical tendencies, no high-affinity analogues were found. As a result, the importance of Arg8 was investigated, and we have demonstrated that this residue might be more involved in binding than previously thought. We successfully synthesised a relaxin-3/chlorotoxin analogue, which appeared to fold correctly. However, the yield following oxidation was poor, and no bioactivity data or structural data confirming the correct fold was obtained within the time limits of the project. A secondary aim was to probe for favourable mutations around the receptor- binding region by synthesising a combinational library. We were able to successfully synthesise a library of peptides with mutations in one position by inserting a mixture of amino acids at this coupling step in the solid phase peptide synthesis (SPPS) procedure. Although no significant improvement in binding was seen for the analogues generated, important methodological advances were made that will be used to scan different positions for new contact points with the receptor. URI: http://hdl.handle.net/10037/3428 File(s) in this item: 1
thesis.pdf (11.68Mb) -
Engeland, Anders; Bjørge, Tone; Daltveit, Anne Kjersti; Skurtveit, Svetlana; Vangen, Siri; Vollset, Stein Emil; Furu, Kari (Journal article; Tidsskriftartikkel; Peer reviewed, 2011)[+][-]
Abstract: This study aimed to use a population-based Prescription Database to explore later development of diabetes in women registered with gestational diabetes mellitus (GDM) and/or preeclampsia in the Medical Birth Registry of Norway (MBRN) during 2004–8. We used two nationwide Norwegian registries, the Norwegian Prescription Database and the MBRN, to explore the onset of later diabetes after pregnancy complications, indicated by receiving prescriptions of drugs used to treat diabetes, in 230,000 women giving birth in 2004–8. The mean follow-up of the study cohort was 3.7 years. Five years after pregnancy, about 19 and 2% of women with GDM and preeclampsia, respectively, received drugs used to treat diabetes, compared to 0.5% of those without these complications. The risk of being dispensed drugs used to treat diabetes within the first years after pregnancy was estimated to be 41 times (95% CI: 35–47) and 3.0 times (95% CI: 2.4–3.6) higher in women with GDM and preeclampsia, respectively, compared to women without these pregnancy complications. Women with pregnancies complicated with preeclampsia or GDM had an increased risk of later diabetes, especially those having GDM. If the increase in frequency of GDM observed inMBRN in recent years is real, a further increase in diabetic women can be expected. URI: http://hdl.handle.net/10037/3901 File(s) in this item: 1
article.pdf (240.9Kb) -
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) -
Engesæter, Birgit Øvstebø; Engebråten, Olav; Flørenes, Vivi Ann; Mælandsmo, Gunhild (Journal article; Tidsskriftartikkel; Peer reviewed, 2012)[+][-]
Abstract: Mapatumumab and lexatumumab (targeting death receptor 4 (DR4) and 5 (DR5), respectively) are agonistic TRAIL receptor antibodies that induce apoptosis in a wide range of cancer cells. The potency of mapatumumab and lexatumumab was assessed in mono therapy protocols, and the ability to sensitize for dacarbazine (DTIC) treatment was explored in ten different melanoma cell lines. Our data indicated that melanoma cell lines tend to be resistant to mapatumumab, most likely due to low expression of DR4, while a dose dependent response to lexatumumab was observed. Combining DTIC and lexatumumab induced an additive or synergistic effect on cell death in the various melanoma cell lines. The synergistic effect observed in the FEMX-1 cell line was related to enhanced cleavage of Bid in parallel with elevated expression of the pro-apoptotic proteins Bim, Bax and Bak. Furthermore, the anti-apoptotic proteins Bcl-XL, cIAP-1, XIAP and livin were down regulated. Cleavage of Bid and down regulation of cIAP-2 and livin were observed in vivo. Altogether, these data suggest a change in the balance between pro- and anti-apoptotic proteins favoring induction of apoptosis. In the more therapy resistant cell line, HHMS, no changes in the pro- and anti-apoptotic proteins were observed. FEMX-1 xenografts treated with DTIC and lexatumumab showed reduced growth and increased level of apoptosis compared to the control groups, providing arguments for further evaluation of this combination in melanoma patients. URI: http://hdl.handle.net/10037/4920 File(s) in this item: 1
article.pdf (1.861Mb) -
Erdal, Hilde (Master thesis; Mastergradsoppgave, May-2008)[+][-]
Abstract: Innledning: Apotekloven slår fast at legemidler skal utleveres nøyaktig etter resept og rekvisisjon. Studier viser imidlertid at feil og mangler forekommer ved 2,0 % av reseptene som blir levert inn ved vanlige apotek i Norge, og forskrivningsavvik forekommer ved 8,5 % av ordinasjonene på resepter utskrevet av leger ved Haukeland Universitetssykehus. Forskrivningsavvik kan medføre fare for klinisk signifikante effekter på pasientens legemiddelbehandling og uønskede legemiddelhendelser. Hensikten med studien var å undersøke hvor stor andel av forskrivningsavvikene som hadde en klinisk relevans for pasientens legemiddelbehandling, og hvor alvorlig den kliniske relevansen var. Metode: Det ble i en studie fra 2007 registrert 867 forskrivningsavvik ved Haukeland Sykehusapotek, Vitusapotek Nordstjernen Bergen og Tønsberg Sykehusapotek. Et ekspertpanel med åtte deltakere, hvorav fire farmasøyter og fire leger, klassifiserte 119 potensielt klinisk relevante avvik i henhold til en modifisert versjon av Safety Assessment Code (SAC)-score med fire kategorier av klinisk relevans. Klassifiseringen ble gjennomført individuelt. Inter-rater reliabilitet ble vurdert i forhold til grad av enighet beregnet ved kappa-statistikk. Resultater: Ekspertpanelet viste svært lav enighet, κ=0,115-0,093, noe som henspeiler lav inter-rater reliabilitet. Dette må tas hensyn til ved tolkning av resultatene. Det er tendenser til at ekspertpanelet vurderte interaksjoner og avvik i forbindelse med dosering, samt legemidler i ATC-gruppe N 02 Analgetika, som mest klinisk relevant. Forskrivningsavvik men klinisk relevans forekom ved 1,29 % av resepter skrevet ut av sykehusleger, og ved 0,33 % av resepter skrevet ut av leger utenfor sykehus. Konklusjon: Klinisk relevante forskrivningsavvik forekommer hyppgere ved resepter skrevet ut av sykehusleger enn resepter utskrevet av leger utenfor sykehus. Metoden som ble benyttet for klassifisering av klinisk relevans av forskrivningsavvik hadde ikke tilfredsstillende reliabilitet og validitet. URI: http://hdl.handle.net/10037/1575 File(s) in this item: 1
thesis.pdf (1.287Mb) -
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
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Eriksen, Sureeporn Aemsangthum (Master thesis; Mastergradsoppgave, 20-May-2012)[+][-]
Abstract: Nasjonalt råd for ernæring anbefaler å spise fisk og sjømat fordi de innholder de flerumettede omega-3 fettsyrene eikosapentaensyre (EPA: 20:5n-3) og dokosahekaensyre (DHA: 22: 6n-3). Mye forskning viser kobling mellom omega-3 fettsyrene og helsegevinster. Helsegevinstene er at disse fettsyrene er betennelsesdempende, de reduserer risiko for å utvikle sykdommer som revmatoid artritt, hjerte -kar sykdommer, psoriasis, og de virker hemmende på utvikling av enkelte mentale lidelser og de reduserer tilfeller prostatakreft. Omega-3 fettsyrer er nødvendig for normal utvikling av fosteret under svangerskapet og er også spesielt viktig for normal nevrologisk utvikling. Mange av verdens kostholdsorganisasjoner anbefaler at man spiser fisk 1-2 ganger i uken eller får i seg 0,2-0,5 g EPA og DHA. Alternative kilder til EPA og DHA er helsekostprodukter. EPA og DHA i produktene bør være av god kvalitet og i riktig mengde for å dekke kroppens behov. Det er derfor viktig at produktdeklarasjon samsvarer med innholdet i produktene. Målet med min oppgave var å undersøke fettklassesammensetningen av Omega-3 produktene; Lofot tran, Trippel Omega-3, Nordic Light krill & fiskeolje, Omega-3 med krillolje (blanding av krill og fiskeolje) og Complete Krillolje (krillolje). I et av blandings produktene av krill & fiskeolje (Nordic Light krill & fiskeolje) ble fettsyresammensetningen undersøkt i noen av fettklassene i produktet. Tilslutt ble det målt frie fettsyrer av de to krill & fiskeoljeproduktene i 2 perioder for å se stabilitet ved lagring. Resultatene viste at Lofot tran inneholdt triacylglyserider; Trippel Omega-3 innehold metyl- og etylestere; Nordic Light krill & fiskeolje innholdt polare lipider, kolesterol, diacylglyserider, frie fettsyrer og triacylglyserider; Omega-3 med krillolje (blanding av krill og fiskeolje) inneholdt triacylglyserider, metyl og etylester. Det siste produktet som ble undersøkt var Complete Krilloljeproduktet som inneholdt tilsvarende fettklasser som Nordic light krill & fiskeolje, men med mer polare lipider og frie fettsyrer. Ved undersøkelse av fettsyresammensetningen i Nordic Light krill & fiskeolje, viste denne et innhold av omega-3 (n-3) 63.9 %, omega-6 (n-6) 3.2 %, og langkjedede flerumettede omega-3 (Lc n-3) 63,2 %. EPA var 31,8 % og DHA 26 %. Ved lagring av Krill & fiske olje produktene i romtemperatur i ca 2 måneder vistes en viss forskjell i verdiene av de frie fettsyrene, men ikke noe som kan karakteriseres som dramatisk økning. URI: http://hdl.handle.net/10037/4325 File(s) in this item: 1
thesis.pdf (1.382Mb)
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