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Artikler, rapporter og annet (farmasi)
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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) -
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) -
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) -
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
article.pdf (662.6Kb) -
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
article.pdf (502.4Kb)
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