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Browsing Artikler, rapporter og annet (farmasi) by Title
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Kiselev, Yury; Eriksen, Tonje Engevik; Forsdahl, Siri; Nguyen, Lan Huong Thi; Mikkola, Ingvild (Journal article; Tidsskriftartikkel; Peer reviewed, 2012)[+][-]
Abstract: Pax6 and Pax6(5a) are two isoforms of the evolutionary conserved Pax6 gene often co-expressed in specific stochiometric relationship in the brain and the eye during development. The Pax6(5a) protein differs from Pax6 by having a 14 amino acid insert in the paired domain, causing the two proteins to have different DNA binding specificities. Difference in functions during development is proven by the fact that mutations in the 14 amino acid insertion for Pax6(5a) give a slightly different eye phenotype than the one described for Pax6. Whereas quite many Pax6 target genes have been published during the last years, few Pax6(5a) specific target genes have been reported on. However, target genes identified by Pax6 knockout studies can probably be Pax6(5a) targets as well, since this isoform also will be affected by the knockout. In order to identify new Pax6 target genes, and to try to distinguish between genes regulated by Pax6 and Pax6(5a), we generated FlpIn-3T3 cell lines stably expressing Pax6 or Pax6(5a). RNA was harvested from these cell lines and used in gene expression microarrays where we identified a number of genes differentially regulated by Pax6 and Pax6(5a). A majority of these were associated with the extracellular region. By qPCR we verified that Ncam1, Ngef, Sphk1, Dkk3 and Crtap are Pax6(5a) specific target genes, while Tgfbi, Vegfa, EphB2, Klk8 and Edn1 were confirmed as Pax6 specific target genes. Nbl1, Ngfb and seven genes encoding different glycosyl transferases appeared to be regulated by both. Direct binding to the promoters of Crtap, Ctgf, Edn1, Dkk3, Pdgfb and Ngef was verified by ChIP. Furthermore, a change in morphology of the stably transfected Pax6 and Pax6(5a) cells was observed, and the Pax6 expressing cells were shown to have increased proliferation and migration capacities. URI: http://hdl.handle.net/10037/4107 File(s) in this item: 1
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Sakshaug, Solveig; Hartz, Ingeborg; Furu, Kari; Skurtveit, Svetlana; Engeland, Anders; Eggen, Anne Elise; Njølstad, Inger (Journal article; Tidsskriftartikkel; Peer reviewed, 05-Dec-2007)[+][-]
Abstract: Background: A previous study has shown that variations in threshold and intensity (lipid goal attainment) of statins for primary prevention contribute to regional differences in overall consumption of statins in Norway. Our objective was to explore how differences in prevalences of use, dosing characteristics, choice of statin and continuity of therapy in individual patients adds new information to previous results. Methods: Data were retrieved from The Norwegian Prescription Database. We included individuals from counties with high, average, and low statin consumption, who had at least one statin prescription dispensed during 2004 (N = 40 143). 1-year prevalence, prescribed daily dose (PDD), statin of choice, and continuity of therapy assessed by mean number of tablets per day. Results: The high-consumption county had higher prevalence of statin use in all age groups. Atorvastatin and simvastatin were dispensed in 79–87% of all statin users, and the proportion was significantly higher in the high-consumption county. The estimated PDDs were higher than the DDDs, up to twice the DDD for atorvastatin. The highconsumption county had the highest PDD for simvastatin (25.9 mg) and atorvastatin (21.9 mg), and more users received tablets in the upper range of available strengths. Continuity of therapy was similar in the three counties. Conclusion: Although differences in age-distribution seems to be an important source of variation in statin consumption, it cannot account for the total variation between counties in Norway. Variations in prevalences of use, and treatment intensity in terms of PDD and choice of statin also affect the total consumption. The results in this study seems to correspond to previous findings of more frequent statin use in primary prevention, and more statin users achieving lipid goal in the highest consuming county. URI: http://hdl.handle.net/10037/1388 File(s) in this item: 1
article.pdf (281.7Kb) -
Townsend, Jeffrey P.; Bøhn, Thomas; Nielsen, Kaare Magne (Journal article; Tidsskriftartikkel; Peer reviewed, 2012)[+][-]
Abstract: Experimental approaches to identify horizontal gene transfer (HGT) events of non-mobile DNA in bacteria have typically relied on detection of the initial transformants or their immediate offspring. However, rare HGT events occurring in large and structured populations are unlikely to be detected in a short time frame. Population genetic modeling of the growth dynamics of bacterial genotypes is therefore necessary to account for natural selection and genetic drift during the time lag and to predict realistic time frames for detection with a given sampling design. Here we draw on statistical approaches to population genetic theory to construct a cohesive probabilistic framework for investigation of HGT of exogenous DNA into bacteria. In particular, the stochastic timing of rare HGT events is accounted for. Integrating over all possible event timings, we provide an equation for the probability of detection, given that HGT actually occurred. Furthermore, we identify the key variables determining the probability of detecting HGT events in four different case scenarios that are representative of bacterial populations in various environments. Our theoretical analysis provides insight into the temporal aspects of dissemination of genetic material, such as antibiotic resistance genes or transgenes present in genetically modified organisms. Due to the long time scales involved and the exponential growth of bacteria with differing fitness, quantitative analyses incorporating bacterial generation time, and levels of selection, such as the one presented here, will be a necessary component of any future experimental design and analysis of HGT as it occurs in natural settings. URI: http://hdl.handle.net/10037/4186 File(s) in this item: 1
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Ernst, Thomas; Gruber, Franz; Pelz-Ackermann, Oliver; Mikkola, ingvild; Maier, J; Pfirrmann, M; Muller, MC; Porkka, Kimmo; Niederwieser, D; Hochhaus, A; Lange, T (Journal article; Tidsskriftartikkel; Peer reviewed, 2009)[+][-]
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Starikova, Irina; Harms, Klaus; Haugen, Pål; Lunde, Tracy Munthali; Primicerio, Raul; Samuelsen, Ørjan; Nielsen, Kaare Magne; Johnsen, Pål Jarle (Journal article; Tidsskriftartikkel; Peer reviewed, 2012)[+][-]
Abstract: Horizontal gene transfer (HGT) plays a major role in bacterial microevolution as evident from the rapid emergence and spread of antimicrobial drug resistance. Few studies have however addressed the population dynamics of newly imported genetic elements after HGT. Here, we show that newly acquired class-1 integrons from Salmonella enterica serovar Typhimurium and Acinetobacter baumannii, free of associated transposable elements, strongly reduce host fitness in Acinetobacter baylyi. Insertional inactivation of the integron intI1 restored fitness, demonstrating that the observed fitness costs were due to the presence of an active integrase. The biological cost of harboring class-1 integrons was rapidly reduced during serial transfers due to intI1 frameshift mutations leading to inactivated integrases. We use a mathematical model to explore the conditions where integrons with functional integrases are maintained and conclude that environmental fluctuations and episodic selection is necessary for the maintenance of functional integrases. Taken together, the presented data suggest a trade-off between the ability to capture gene cassettes and long-term stability of integrons and provide an explanation for the frequent observation of inactive integron-integrases in bacterial populations. URI: http://hdl.handle.net/10037/4776 File(s) in this item: 1
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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
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Vasskog, Terje; Andersen, Jeanette hammer; Hansen, Espen; Svenson, Johan (Journal article; Tidsskriftartikkel; Peer reviewed, 2012)[+][-]
Abstract: The marine opisthobranch Scaphander lignarius has been analyzed in the systematic search for novel bioactive compounds in Arctic marine organisms using bioassay guided fractionation. A number of highly cytotoxic fractions were shown to contain mainly polyunsaturated fatty acids (PUFAs). Selected PUFAs were isolated and identified using both liquid chromatography-mass spectrometry (LC-MS) and nuclear magnetic resonance (NMR). It was shown that the opisthobranch contained unusual PUFAs such as several ω3 fatty acids and the ω7 heneicosa-5,8,11,14-tetraenoic acid (21:4 n-7) not isolated before. The organism was shown to be a very rich source of PUFAs and the activity of the isolated compounds against a range of human cancer cell lines (melanoma, colon carcinoma and breast carcinoma) is further reported. The ω7 PUFA was significantly more cytotoxic in comparison with reference ω6 arachidonic and ω3 eicosapentaenoic acid. A noteworthy non-selective cytotoxicity against normal lung fibroblasts was also established. The paper contains isolation protocols in addition to cytotoxicity data of the isolated compounds. The potential of marine mollusks as a source for rare PUFAs is also discussed. URI: http://hdl.handle.net/10037/4918 File(s) in this item: 1
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Zeiss, Daniel Horst; Wagner, Marita; Bauer-Brandl, Annette (Journal article; Tidsskriftartikkel; Peer reviewed, 2009)[+][-]
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Tekle, Yonas I.; Nielsen, Kaare Magne; Liu, Jingzhou; Pettigrew, Melinda M.; Meyers, Lauren A.; Galvani, Alison P.; Townsend, Jeffrey P. (Journal article; Tidsskriftartikkel; Peer reviewed, 2012)[+][-]
Abstract: Vaccination has proven effective in controlling many infectious diseases. However, differential effectiveness with regard to pathogen genotype is a frequent reason for failures in vaccine development. Often, insufficient immune response is induced to prevent infection by the diversity of existing serotypes present in pathogenic populations of bacteria. These vaccines that target a too narrow spectrum of serotypes do not offer sufficient prevention of infections, and can also lead to undesirable strain replacements. Here, we examine a novel idea to specifically exploit the narrow spectrum coverage of some vaccines to combat specific, emerging multi- and pan-resistant strains of pathogens. Application of a narrow-spectrum vaccine could serve to prevent infections by some strains that are hard to treat, rather than offer the vaccinated individual protection against infections by the pathogenic species as such. We suggest that vaccines targeted to resistant serotypes have the potential to become important public health tools, and would represent a new approach toward reducing the burden of particular multi-resistant strains occurring in hospitals. Vaccines targeting drug-resistant serotypes would also be the first clinical intervention with the potential to drive the evolution of pathogenic populations toward drug-sensitivity. We illustrate the feasibility of this approach by modeling a hypothetical vaccine that targets a subset of methicillin-resistant Staphylococcus aureus (MRSA) genotypes, in combination with drug treatment targeted at drug-sensitive genotypes. We find that a combined intervention strategy can limit nosocomial outbreaks, even when vaccine efficacy is imperfect. The broader utility of vaccine-based resistance control strategies should be further explored taking into account population structure, and the resistance and transmission patterns of the pathogen considered. URI: http://hdl.handle.net/10037/4916 File(s) in this item: 1
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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
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Slipicevic, Ana; Holm, Ruth; Emilsen, Elisabeth; Rosnes, Anne Katrine Ree; Welch, Danny R.; Mælandsmo, Gunhild; Flørenes, Vivi Ann (Journal article; Tidsskriftartikkel; Peer reviewed, 2012)[+][-]
Abstract: Breast cancer metastasis suppressor 1 (BRMS1) blocks metastasis in melanoma xenografts; however, its usefulness as a biomarker in human melanomas has not been widely studied. The goal was to measure BRMS1 expression in benign nevi, primary and metastatic melanomas and evaluate its impact on disease progression and prognosis. Paraffin-embedded tissue from 155 primary melanomas, 69 metastases and 15 nevi was examined for BRMS1 expression using immunohistochemistry. siRNA mediated BRMS1 down-regulation was used to study impact on invasion and migration in melanoma cell lines. A significantly higher percentage of nevi (87%), compared to primary melanomas (20%) and metastases (48%), expressed BRMS1 in the nucelus (p < 0.0001). Strong nuclear staining intensity was observed in 67% of nevi, and in 9% and 24% of the primary and metastatic melanomas, respectively (p < 0.0001). Comparable cytoplasmic expression was observed (nevi; 87%, primaries; 86%, metastases; 72%). However, a decline in cytoplasmic staining intensity was observed in metastases compared to nevi and primary tumors (26%, 47%, and 58%, respectively, p < 0.0001). Score index (percentage immunopositive celles multiplied with staining intensity) revealed that high cytoplasmic score index (≥ 4) was associated with thinner tumors (p = 0.04), lack of ulceration (p = 0.02) and increased disease-free survival (p = 0.036). When intensity and percentage BRMS1 positive cells were analyzed separately, intensity remained associated with tumor thickness (p = 0.024) and ulceration (p = 0.004) but was inversely associated with expression of proliferation markers (cyclin D3 (p = 0.008), cyclin A (p = 0.007), and p21Waf1/Cip1 (p = 0.009)). Cytoplasmic score index was inversely associated with nuclear p-Akt (p = 0.013) and positively associated with cytoplasmic p-ERK1/2 expression (p = 0.033). Nuclear BRMS1 expression in ≥ 10% of primary melanoma cells was associated with thicker tumors (p = 0.016) and decreased relapse-free period (p = 0.043). Nuclear BRMS1 was associated with expression of fatty acid binding protein 7 (FABP7; p = 0.011), a marker of invasion in melanomas. In line with this, repression of BRMS1 expression reduced the ability of melanoma cells to migrate and invade in vitro. Our data suggest that BRMS1 is localized in cytoplasm and nucleus of melanocytic cells and that cellular localization determines its in vivo effect. We hypothesize that cytoplasmic BRMS1 restricts melanoma progression while nuclear BRMS1 possibly promotes melanoma cell invasion. URI: http://hdl.handle.net/10037/4904 File(s) in this item: 1
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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) -
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
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Høye, Anne; Jacobsen, Bjarne K.; Hansen, Vidje (Journal article; Tidsskriftartikkel; Peer reviewed, 2011)[+][-]
Abstract: A study of mortality for all patients with schizophrenia admitted to the University Hospital of North Norway during 1980-2006 was performed, with a special focus on gender differences and changes in mortality during a period of transition from hospital-based to community-based care. A total of 1111 patients with schizophrenia were included, and the cohort was linked to the Causes of Death Register of Norway. Males and females had 3.5 and 2.6 times, respectively, higher mortality than the general population. The standardized mortality ratios were higher during the last nine years than the first nine years, and for women admitted after 1992, we found evidence for an increasing difference in mortality compared to the general female population as well as an increase in absolute mortality. In the subgroup of patients who had always been admitted voluntarily, women tended to have higher mortality, and a particularly high standardized mortality rate (SMR) was found in this group of female schizophrenic patients. Our results confirmed a persisting mortality gap between patients with schizophrenia and the general population over a period of 27 years, with a tendency of increasing standardized mortality ratios over time. The SMR for total mortality of women with schizophrenia is rising and becoming just as high as for men, both for unnatural and natural causes of death. URI: http://hdl.handle.net/10037/4096 File(s) in this item: 1
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Okeke, Malachy Ifeanyi; Tryland, Morten; Nilssen, Øivind; Moens, Ugo; Traavik, Terje (Journal article; Tidsskriftartikkel; Peer reviewed, 12-May-2009)[+][-]
Abstract: Background: Poxvirus-vectored vaccines against infectious diseases and cancer are currently under development. We hypothesized that the extensive use of poxvirus-vectored vaccine in future might result in co-infection and recombination between the vaccine virus and naturally occurring poxviruses, resulting in hybrid viruses with unpredictable characteristics. Previously, we confirmed that co-infecting in vitro a Modified vaccinia virus Ankara (MVA) strain engineered to express influenza virus haemagglutinin (HA) and nucleoprotein (NP) genes with a naturally occurring cowpox virus (CPXV-NOH1) resulted in recombinant progeny viruses (H Hansen, MI Okeke, Ø Nilssen, T Traavik, Vaccine 23: 499–506, 2004). In this study we analyzed the biological properties of parental and progeny hybrid viruses.
Results: Five CPXV/MVA progeny viruses were isolated based on plaque phenotype and the expression of influenza virus HA protein. Progeny hybrid viruses displayed in vitro cell line tropism of CPXV-NOH1, but not that of MVA. The HA transgene or its expression was lost on serial passage of transgenic viruses and the speed at which HA expression was lost varied with cell lines. The HA transgene in the progeny viruses or its expression was stable in African Green Monkey derived Vero cells but became unstable in rat derived IEC-6 cells. Hybrid viruses lacking the HA transgene have higher levels of virus multiplication in mammalian cell lines and produced more enveloped virions than the transgene positive progenitor virus strain. Analysis of the subcellular localization of the transgenic HA protein showed that neither virus strain nor cell line have effect on the subcellular targets of the HA protein. The influenza virus HA protein was targeted to enveloped virions, plasma membrane, Golgi apparatus and cytoplasmic vesicles.
Conclusion: Our results suggest that homologous recombination between poxvirus-vectored vaccine and naturally circulating poxviruses, genetic instability of the transgene, accumulation of non-transgene expressing vectors or hybrid virus progenies, as well as cell line/type specific selection against the transgene are potential complications that may result if poxvirus vectored vaccines are extensively used in animals and man.URI: http://hdl.handle.net/10037/2191 File(s) in this item: 1
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Karn, Pankaj Ranjan; Vanic, Zeljka; Pepic, Ivan; Skalko-Basnet, Natasa (Journal article; Tidsskriftartikkel; Peer reviewed, 2011)[+][-]
Abstract: Development of liposomal mucoadhesive drug delivery system, which is able to improve the bioavailability of poorly absorbed oral drugs by prolonging their gastric and intestinal residence time, through facilitating the intimate contact of the delivery system with the absorption membrane. Liposomes containing model drug atenolol were prepared by the modified ethanol injection method. Liposomes containing atenolol were coated by different mucoadhesive polymers, for example, chitosan, Carbopol 974P, Eudragit L100, and Eudragit S100, to optimize the choice of coating material. The delivery systems were tested for their in vitro mucoadhesiveness. Liposomes prepared by the ethanol injection method were of satisfactory size (around 100 nm, before coating). Through the coating of liposomes in the presence of unentrapped material, the entrapment efficiency for drug was increased. In vitro mucoadhesive test confirmed the mucoadhesive properties of the coated layer for all tested polymers; however, Eudragit S100-coated liposomes were superior to other coating materials. Eudragit coating appeared to be an optimal polymer choice. These preliminary data indicate that polymer-coated mucoadhesive liposomes are able to carry sufficient amount of drug and to remain attached to the intestinal mucosa for a sufficient period of time to enable prolonged absorption of entrapped drug. While keeping in mind that the in vivo conditions may vary with the in vitro ones, we may recommend the system described in our work for possible oral delivery of peptides and phytochemicals. URI: http://hdl.handle.net/10037/4068 File(s) in this item: 1
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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
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Hurler, Julia; Skalko-Basnet, Natasa (Journal article; Tidsskriftartikkel; Peer reviewed, 2012)[+][-]
Abstract: Chitosan is currently proposed to be one of the most promising polymers in wound dressing development. Our research focuses on its potential as a vehicle for nano-delivery systems destined for burn therapy. One of the most important features of wound dressing is its bioadhesion to the wounded site. We compared the bioadhesive properties of chitosan with those of Carbopol, a synthetic origin polymer. Chitosan-based hydrogels of different molecular weights were first analyzed by texture analysis for gel cohesiveness, adhesiveness and hardness. In vitro release studies showed no difference in release of model antimicrobial drug from the different hydrogel formulations. Bioadhesion tests were performed on pig ear skin and the detachment force, necessary to remove the die from the skin, and the amount of remaining formulation on the skin were determined. Although no significant difference regarding detachment force could be seen between Carbopol-based and chitosan-based formulations, almost double the amount of chitosan formulation remained on the skin as compared to Carbopol formulations. The findings confirmed the great potential of chitosan-based delivery systems in advanced wound therapy. Moreover, results suggest that formulation retention on the ex vivo skin samples could provide deeper insight on formulation bioadhesiveness than the determination of detachment force URI: http://hdl.handle.net/10037/4921 File(s) in this item: 1
article.pdf (359.1Kb) -
Skurtveit, Svetlana; Bachs, Liliana Casulleras; Bramness, Jørgen G.; Engeland, Anders (Journal article; Tidsskriftartikkel; Peer reviewed, 2008)[+][-]
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Johnsen, Pål jarle; Townsend, JP; Bøhn, Thomas; Simonsen, Gunnar Skov; Sundsfjord, arnfinn; Nielsen, Kaare Magne (Journal article; Tidsskriftartikkel; Peer reviewed, 2011)[+][-]
Abstract: To estimate the relative fitness differences between glycopeptide-resistant Enterococcus faecium (GREF) and glycopeptide-susceptible E. faecium (GSEF) from yearly surveillance data on the occurrence of GREF in Danish poultry farm environments. A population genetic model was adapted to retrospectively estimate the biological fitness cost of acquired resistance. Maximization of a likelihood function was used to predict the longitudinal persistence of acquired resistance. Our analysis suggests strong selection against GREF following the 1995 ban on the glycopeptide growth promoter avoparcin. However, parameterizing the model with two selection coefficients suggesting a reduced negative effect of the acquired resistance on bacterial fitness over time significantly improved the fit of the model. Our analyses suggest that the acquired glycopeptide resistance will persist for >25 years. Conclusions Acquired resistance determinants in commensal E. faecium populations in Danish farm environments are likely to persist for decades, even in the absence of glycopeptide use. URI: http://hdl.handle.net/10037/3847 File(s) in this item: 1
article.pdf (174.3Kb)
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