| 41. |
- Svensson, Olof, et al.
(författare)
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Interactions between Drug Delivery Particles and Mucin in Solution and at Interfaces
- 2008
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Ingår i: Langmuir. - : American Chemical Society (ACS). - 0743-7463 .- 1520-5827. ; 24, s. 2573-2579
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Tidskriftsartikel (refereegranskat)abstract
- Cubosome particles were produced by fragmenting a cubic crystalline phase of glycerol monooleate and water in the presence of a stabilizing poly(ethylene oxide)-based polymer. The aim of our investigation was to study the interaction between these particles and mucin to gain information on how they would perform as a vehicle for mucosal drug delivery. Particle electrophoresis was used to investigate the interactions between particles and mucin in solution, and ellipsometry was utilized to study the interactions between particles and mucin-coated silica surfaces. The interaction studies were performed at relevant physiological conditions, and the pH and ionic strength were varied to gain more information about the driving forces for the interaction. The results from electrophoretic measurements showed that mucin in solution adsorbed to the particles at pH 4, whereas at pH 6 no clear interaction was detected. From ellipsometric measurements it was evident that the particles adsorb reversibly to a mucin-coated silica surface at pH 4, while no adsorption of particles could be detected at pH 6. The overall conclusion is that the interaction between these particles and mucin is weak and pH-dependent. These findings are in agreement with other investigations of the interactions between mucin and poly(ethylene oxide) chains.
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| 42. |
- Svensson, Olof
(författare)
-
Interactions of Mucins with Biopolymers and Drug Delivery Particles
- 2008
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The main components in the mucous gels apart from water are mucins, which are proteins with high molecular weights and an abundance of negatively charged oligosaccharide side chains. The aim of the investigations was to characterize interactions between mucins and other proteins that are present in the mucous gel, and also between mucins and components used in pharmaceutical formulations. More specifically, the main objectives were (I) to investigate the possibility to assemble multilayer films with mucins and oppositely charged polymers or proteins on solid substrates; (II) to evaluate mucoadhesive proper-ties of drug delivery particles by examination of their interactions with mucins. The construction of multilayer films was performed on silica and hydrophobized silica surfaces by alternate adsorption, and the adsorbed amount and thickness of the films were measured in situ by time resolved ellipsometry. It was demonstrated that films could be assembled using mucins in combination with both chitosan and lactoperoxidase. The build-up was characterized by adsorption and redissolution processes, and the extent of redissolution could be explained by taking the charge densities and concentrations of the components into account. It was also demonstrated that the nature of the substrate can be crucial for the possibilities to assemble multilayer films, and from the results it may be concluded that a high amount of mucin in the first step is important for successful layer-by-layer assembly. Furthermore, it was demonstrated that lactoperoxidase is catalytically active when adsorbed to mucin layers, and it may thereby exert its antimicrobial action. The evaluation of mucoadhesive properties of drug delivery particles was performed with lipid nanoparticles stabilized by a poly(ethylene oxide) based polymer and with particles modified by chitosan. Both types of model particles (unmodified and chitosan modified) were investigated by measuring their adsorption to mucin-coated silica surfaces by ellipsometry. It was shown that the binding of unmodified particles to mucin-coated silica surfaces was weak and pH-dependent. Based on the pH and electrolyte dependence of the adsorption, it was proposed that the interaction is mediated by hydrogen bonding between protonated carboxyl groups in the mucin molecule and oxygen atoms in poly(ethylene oxide). Chitosan modified particles, on the other hand, showed a substantial and strong binding to mucin-coated surfaces, which can probably be attributed to interactions between amino groups in chitosan and negatively charged groups in the mucin layer. The findings from the present investigations are in agreement with previous reports on the interaction of mucins with poly(ethylene oxide) and chitosan. It can therefore be concluded that the methodology applied is useful for evaluating mucoadhesive properties of nanoparticles.
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| 43. |
- Svensson, Olof, et al.
(författare)
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Layer-by-layer assembly of mucin and chitosan - Influence of surface properties, concentration and type of mucin
- 2006
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Ingår i: Journal of Colloid and Interface Science. - : Academic Press. - 0021-9797 .- 1095-7103. ; 299:2, s. 608-616
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Tidskriftsartikel (refereegranskat)abstract
- Bovine submaxillary mucin (BSM) and chitosan were used to build layer-by-layer structures on solid substrates. The build-up was monitored using in situ ellipsometry to obtain time resolved values of the thickness and adsorbed amount. Additionally surface morphology during build-up was studied by atomic force microscopy (AFM). It was found that the adsorbed amount of the film increases approximately linearly with each deposition cycle on hydrophobized silica whereas construction on silica was found not to be possible at the experimental conditions used. We conclude that sufficient amount of the first mucin layer is crucial for the subsequent multilayer formation. The complex build-up kinetics on hydrophobized silica is characterized by adsorption and redissolution processes and the overall growth is the sum of both processes. AFM imaging on hydrophobized silica also confirmed the presence of redissolution processes and chitosan addition led to a reduction both in the number of surface aggregates and in the roughness of the surface. The present work also shows that by adjusting the relative concentrations of the polyelectrolytes it is possible to change the growth rate considerably. The final structures after deposition of 8 bilayers were found to have a high content of water and film stability test revealed that a substantial amount dissolves when increasing electrolyte concentration or pH of the ambient solution. Human mucin from saliva (MUC5B) was also used to create multilayers with chitosan on hydrophobized silica and it was revealed that no redissolution appears to be present in this system.
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| 44. |
- Svensson, Olof, 1965-, et al.
(författare)
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On the sharpness of the Stolz approach
- 2006
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Ingår i: Annales Academiae Scientiarum Fennicae Mathematica. - 1239-629X .- 1798-2383. ; 31:1, s. 47-59
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Tidskriftsartikel (refereegranskat)abstract
- We study the sharpness of the Stolz approach for the a.e. convergence of functions in the Hardy spaces in the unit disc, first settled in the rotation invariant case by J. E. Littlewood in 1927 and later examined, under less stringent, quantitative hypothesis, by H. Aikawa in 1991. We introduce a new regularity condition, of a qualitative type, under which we prove a version of Littlewood's theorem for tangential approach whose shape may vary from point to point. Our regularity condition can be extended in those contexts where no group is involved, such as NTA domains in Rn. We show exactly in what sense our regularity condition is sharp.
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| 45. |
- Svensson, Per-Olof, et al.
(författare)
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A sensor circuit using reference-based conductance switching in organic electrochemical transistors
- 2008
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Ingår i: Applied Physics Letters. - : AIP Publishing. - 0003-6951 .- 1077-3118. ; 93:20, s. 203301-
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Tidskriftsartikel (refereegranskat)abstract
- Using organic electrochemical transistors as sensors, the sample-receptor reaction often induces moderate changes only in the drain current dynamics as the gate voltage level is switched. Here, we report an electrochemical sensor circuit including electrochemical transistors based on poly(3,4-ethylenedioxythiophene) doped with polystyrenesulfonate that puts out a static sensor response signal. The circuit includes a sample and a reference transistor that are both driven in the resistive mode at 0.1 V. Measurements were performed on aqueous salt electrolytes ranging from 100 to 500 mM concentrations. The signal-ON sensor circuit provides a tenfold increase in the sensitivity as compared to single transistor sensors.
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| 46. |
- Tagesson, Torbjörn, et al.
(författare)
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Does auditor rotation influence audit quality : the contested hypotheses tested on Swedish data
- 2006
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Bok (övrigt vetenskapligt/konstnärligt)abstract
- Auditor independence is considered a key factor when ensuring high audit quality. Advocates for auditor rotation argue that rotation improves audit quality due to its positive influence on auditor independence. Opponents argue that rotation does not lead to improved audit quality, since the independence is gained at the expense of the auditors’ knowledge of business structure and routines. The aim of our study is to investigate the relationship between rotation and audit quality. We use agency theory to derive the advocate view and stewardship theory to derive the opponents’ hypothesis. These hypotheses were tested on Swedish data. The results indicate only weak support for the hypothesis that rotation influence audit quality. The weakness is partly due to measurement problems. The proxies used in the literature appear to measure different facets of audit quality. Through an interpretation of a factor analysis, we suggest two main facets, perceived audit quality, which is significantly influenced by auditor rotation, and actual audit quality, which is not influenced by rotation.
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| 47. |
- Thorven, Maria, et al.
(författare)
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A homozygous nonsense mutation (428G ->A) in the human secretor (FUT2) gene provides resistance to symptomatic norovirus (GGII) infections
- 2005
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Ingår i: Journal of Virology. - 0022-538X .- 1098-5514. ; 79:24, s. 15351-5
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Tidskriftsartikel (refereegranskat)abstract
- Noroviruses (formerly Norwalk-like viruses) are a major cause of acute gastroenteritis worldwide and are associated with a significant number of nosocomial and food-borne outbreaks. In this study we show that the human secretor FUT2 gene, which codes for an alpha(1,2)-fucosyltransferase synthesizing the H-type 1 antigen in saliva and mucosa, is associated with susceptibility to norovirus infections. Allelic polymorphism characterization at nucleotide 428 for symptomatic (n = 53) and asymptomatic (n = 62) individuals associated with nosocomial and sporadic norovirus outbreaks revealed that homozygous nonsense mutation (428G-->A) in FUT2 segregated with complete resistance for the disease. Of all symptomatic individuals, 49% were homozygous (SeSe) and 51% heterozygous (Sese428) secretors, and none were secretor negative (se428se428), in contrast to 20% nonsecretors (se428se428) among Swedish blood donors (n = 104) (P < 0.0002) and 29% for asymptomatic individuals associated with nosocomial outbreaks (P < 0.00001). Furthermore, saliva from secretor-positive and symptomatic patients but not from secretor-negative and asymptomatic individuals bound the norovirus strain responsible for that particular outbreak. This is the first report showing that the FUT2 nonsecretor (se428se428) genotype is associated with resistance to nosocomial and sporadic outbreaks with norovirus.
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| 48. |
- Wikström, Per-Olof, et al.
(författare)
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Why are English youths more violent than Swedish youths? A comparative study of the role of crime propensity, lifestyles and their interactions in two cities
- 2008
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Ingår i: European Journal of Criminology. - : SAGE Publications. - 1477-3708 .- 1741-2609. ; 5:3, s. 309-330
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Tidskriftsartikel (refereegranskat)abstract
- Most cross-national studies of crime and violence explore variation in levels of crime without empirically addressing the causes of these variations. Drawing upon the theoretical framework of the situational action theory of crime causation (e.g. Wikström 2006), in this study we aim to explore and test whether the difference in levels of violence among young people in England and Sweden can be explained (fully or partly) by country differences in young people's crime propensities and lifestyles and their interaction. To achieve this we use data from the English Peterborough Youth Study and the Swedish Eskilstuna Youth Study. The findings show that in both cities (1) young people's self-reported violent behaviour is predicted by crime propensity and lifestyle, and their interaction, and (2) a substantial proportion (40 percent) of the difference in the level of violence vanishes when taking into account national differences in young people's crime propensity and lifestyles. We conclude that the findings support the notion that one major cause of the difference in the level of violence among young people in England and Sweden is that more young people in England have a higher crime propensity and are living criminogenic lifestyles than in Sweden.
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| 49. |
- Yilmaz, Aylin, 1974, et al.
(författare)
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Cerebrospinal fluid HIV-1 RNA, intrathecal immunoactivation, and drug concentrations after treatment with a combination of saquinavir, nelfinavir, and two nucleoside analogues: the M61022 study.
- 2006
-
Ingår i: BMC infectious diseases. - : Springer Science and Business Media LLC. - 1471-2334. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The way various antiretroviral drugs and drug combinations affect HIV-1 infection in the central nervous system is still largely unknown. The aim of this study was to determine the cerebrospinal fluid (CSF) steady-state concentrations of saquinavir and nelfinavir in relation to plasma concentrations, and to study their effect in combination with two nucleoside reverse transcriptase inhibitors (NRTIs) on CSF viral loads, intrathecal immunoactivation, and blood-brain barrier integrity. METHODS: Paired CSF and plasma samples from 8 antiretroviral-naïve HIV-1 infected patients starting combination therapy with saquinavir, nelfinavir, and two nucleoside analogues were collected prior to treatment, and again after approximately 12 and 48 weeks of antiretroviral therapy. Additional plasma samples were taken at weeks 2, 4, 8, 24, and 36. The concentrations of protease inhibitors were analysed, as were levels of HIV-1 RNA, CD4+ T-cell count, beta2-microglobulin, neopterin, albumin ratio, IgG index, and monocytic cell count. RESULTS: None of the patients in the study presented with HIV-1 RNA < 50 copies/mL in CSF or plasma prior to treatment, compared to 5/7 at the end of the study. Signs of cell-mediated intrathecal immunoactivation, measured by neopterin and beta2-microglobulin, decreased significantly in both CSF and serum, although only 1/7 reached normal CSF neopterin levels after 48 weeks of treatment. There was no significant reduction of albumin ratio, IgG index or CSF monocytic cell count. Saquinavir median (range) concentrations were < 2.5 (< 2.5-96.0) nM unbound in plasma, and < 2.5 (< 2.5-9.0) nM total in CSF. Nelfinavir median (range) concentrations were 10.0 (< 2.0-31.0) nM unbound in plasma, and < 2.0 (< 2.0-23.0) nM total in CSF. Saquinavir and nelfinavir were detectable in 7/15 and 9/15 CSF samples, respectively. CONCLUSION: Saquinavir and nelfinavir, in combination with two NRTIs, decrease the CSF viral load and, to a lesser extent, intrathecal immunoactivation. We found reasonably high CSF concentrations of nelfinavir, but suboptimal concentrations of saquinavir.
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| 50. |
- Öberg, Martin, et al.
(författare)
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Thermosensitivity in a reconstructed microtic ear.
- 2008
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Ingår i: Scandinavian Journal of Plastic and Reconstructive Surgery and Hand Surgery. - : Informa UK Limited. - 1651-2073 .- 0284-4311. ; 42:4, s. 190-193
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to evaluate thermo-thresholds in autologous reconstructed microtic ears. Nineteen patients with unilateral microtia were investigated no less than two years after the last operation (3.6+/-1.7 years). Their normal corresponding ear acted as controls. Eight healthy children were also investigated to illustrate technical differences between measuring the two sides. Thermal sensitivity was tested quantitatively using a SENSELab MSA Thermotest. The skin temperature was also tested. Three different areas of the ear were examined: the lobe, the antihelix, and the helix. The reconstructed ear had a significantly higher skin temperature for all investigated areas compared with the normal ear (reconstructed ear 30.2+/-1.2 degrees C, normal ear 28.6+/-0.9 degrees C). For the controls there were no significant differences in any area. For the patients there were small differences in perception of cold between the reconstructed and the normal ear. There were significant differences in the antihelix region and the helix in heat perception in the reconstructed ear compared with the normal one (helix reconstructed ear 43.9+/-3.8 degrees C, helix normal ear 38.3+/-3.0 degrees C, antihelix reconstructed ear 39.9+/-3.0 degrees C, antihelix normal ear 36.4+/-1.7 degrees C). The reconstructed ear had a changed thermosensitivity, but there did not seem to be any clinical disadvantages.
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