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- Bergström, Christel A. S., et al.
(författare)
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Early pharmaceutical profiling to predict oral drug absorption : Current status and unmet needs
- 2014
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Ingår i: European Journal of Pharmaceutical Sciences. - : Elsevier BV. - 0928-0987 .- 1879-0720. ; 57, s. 173-199
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Tidskriftsartikel (refereegranskat)abstract
- Preformulation measurements are used to estimate the fraction absorbed in vivo for orally administered compounds and thereby allow an early evaluation of the need for enabling formulations. As part of the Oral Biopharmaceutical Tools (OrBiTo) project, this review provides a summary of the pharmaceutical profiling methods available, with focus on in silica and in vitro models typically used to forecast active pharmaceutical ingredient's (APIs) in vivo performance after oral administration. An overview of the composition of human, animal and simulated gastrointestinal (GI) fluids is provided and state-of-the art methodologies to study API properties impacting on oral absorption are reviewed. Assays performed during early development, i.e. physicochemical characterization, dissolution profiles under physiological conditions, permeability assays and the impact of excipients on these properties are discussed in detail and future demands on pharmaceutical profiling are identified. It is expected that innovative computational and experimental methods that better describe molecular processes involved in vivo during dissolution and absorption of APIs will be developed in the OrBiTo. These methods will provide early insights into successful pathways (medicinal chemistry or formulation strategy) and are anticipated to increase the number of new APIs with good oral absorption being discovered. (C) 2013 Elsevier B.V. All rights reserved.
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| 4. |
- Bergström, Lennart Magnus, et al.
(författare)
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Correlation between the geometrical shape and growth behaviour of surfactant micelles investigated with small-angle neutron scattering
- 2014
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Ingår i: Soft Matter. - : Royal Society of Chemistry (RSC). - 1744-683X .- 1744-6848. ; 10:46, s. 9362-9372
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Tidskriftsartikel (refereegranskat)abstract
- The correlation between the growth behaviour and geometrical shape for CTAB-rich mixed micelles formed by the cationic surfactant hexadecyl trimethyl ammonium bromide (CTAB) and the anionic surfactant sodium octyl sulphate (SOS) has been investigated with small-angle neutron scattering (SANS). Small tablet-shaped micelles formed by CTAB are found to grow only weakly in size with increasing surfactant concentration. The extent of growth becomes increasingly stronger as the fraction of SOS is increased. At higher fractions of SOS, a rather weak growth at low surfactant concentrations is followed by a sharp increase in aggregation numbers beyond a certain surfactant concentration. Such an abrupt transition from weakly to strongly growing micelles has been observed in the past for several micellar systems and is usually referred to as the second critical micelle concentration. The growth behaviour has been rationalized from a theoretical point of view by means of employing the recently developed general micelle model. The theory excellently predicts micellar growth behaviours as well as the observed correlation between the geometrical shape and micellar growth. In accordance, both width and length are found to slightly increase for weakly growing tablet-shaped micelles. On the other hand, strongly growing micelles that are observed above the second cmc display a completely different behaviour, according to which the length increases considerably while the width of the micelles decreases. Most interestingly, by means of optimizing the agreement between the general micelle model and experimentally determined aggregation numbers, we are able to determine the three bending elasticity constants: spontaneous curvature, bending rigidity and saddle-splay constant.
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| 5. |
- Bergström, L. Magnus, et al.
(författare)
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Self-assembly in mixtures of an anionic and a cationic surfactant : A comparison between small-angle neutron scattering and cryo-transmission electron microscopy
- 2013
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Ingår i: Langmuir. - : American Chemical Society (ACS). - 0743-7463 .- 1520-5827. ; 29:38, s. 11834-11848
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Tidskriftsartikel (refereegranskat)abstract
- The self-assembly in SOS-rich mixtures of the anionic surfactant sodium octyl sulfate (SOS) and the cationic surfactant hexadecyltrimethylammonium bromide (CTAB) has been investigated with the complementary techniques small-angle neutron scattering (SANS) and cryo-transmission electron microscopy (cryo-TEM). Both techniques confirm the simultaneous presence of open and closed bilayer structures in highly diluted samples as well as the existence of small globular and large elongated micelles at higher concentrations. However, the two techniques sometimes differ with respect to which type of aggregates is present in a particular sample. In particular, globular or wormlike micelles are sometimes observed with cryo-TEM in the vicinity of the micelle-to-bilayer transition, although only bilayers are present according to SANS and the samples appear bluish to the eye. A similar discrepancy has previously been reported but could not be satisfactorily rationalized. On the basis of our comparison between in situ (SANS) and ex situ (cryo-TEM) experimental techniques, we suggest that this discrepancy appears mainly as a result of the non-negligible amount of surfactant adsorbed at interfaces of the thin sample film created during the cryo-TEM specimen preparation. Moreover, from our detailed SANS data analysis, we are able to observe the unusually high amount of free surfactant monomers present in SOS-rich mixtures of SOS and CTAB, and the experimental results give excellent agreement with model calculations based on the Poisson-Boltzmann mean field theory. Our careful comparison between model calculations and experiments has enabled us to rationalize the dramatic microstructural transformations frequently observed upon simply diluting mixtures of an anionic and a cationic surfactant.
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| 6. |
- Besharat Pour, M, et al.
(författare)
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Effect of parental migration background on childhood nutrition, physical activity, and body mass index
- 2014
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Ingår i: Journal of obesity. - : Hindawi Limited. - 2090-0716 .- 2090-0708. ; 2014, s. 406529-
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Tidskriftsartikel (refereegranskat)abstract
- Background. Poor nutrition, lack of physical activity, and obesity in children have important public health implications but, to date, their effects have not been studied in the growing population of children in Sweden with immigrant parents.Methods. We estimated the association between parental migration background and nutrition, physical activity, and weight in 8-year-old children born in Stockholm between 1994 and 1996 of immigrants and Swedish parents (n=2589). Data were collected through clinical examination and questionnaires filled out by parents. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated using multivariable logistic regression.Results. Children of immigrants complied more closely with Nordic Nutrition Recommendations compared with those of Swedes (OR = 1.35, 95% CI 1.11–1.64). They had higher intake of dietary fibre, vitamins C, B6, and E, folic acid, and polyunsaturated fatty acids (omega-3 and omega-6) reflecting higher consumption of foods of plant origin, but lower intake of vitamins A and D, calcium, and iron reflecting lower consumption of dairy products. Children of immigrants had higher intake of sucrose reflecting higher consumption of sugar and sweets. Furthermore, these children had a higher risk of having low physical activity (OR = 1.31, 95% CI 1.06–1.62) and being overweight (OR = 1.33, 95% CI 1.06–1.65) compared with children of Swedish parents. The odds of having low physical activity and being overweight were even higher in children whose parents were both immigrants. A low level of parental education was associated with increased risk of low physical activity regardless of immigration background.Conclusions. Culturally appropriate tools to capture the diverse range of ethnic foods and other lifestyle habits are needed. Healthcare professionals should be aware of the low levels of physical activity, increased weight, and lack of consumption of some important vitamins among children of immigrants.
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| 7. |
- D'Arrigo, I., et al.
(författare)
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Diverse IgG serum response to novel glycopeptide epitopes detected within immunodominant stretches of Epstein-Barr virus glycoprotein 350/220: diagnostic potential of O-glycopeptide microarrays
- 2013
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Ingår i: Glycoconjugate Journal. - : Springer Science and Business Media LLC. - 0282-0080 .- 1573-4986. ; 30:7, s. 633-640
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Tidskriftsartikel (refereegranskat)abstract
- The Epstein-Barr virus (EBV) envelope glycoprotein 350/220 (gp350/220) is the most abundant molecule on the viral surface and it is responsible for the initial viral attachment to cell surface of the host. As many other viral envelope proteins, it is highly glycosylated, not least with O-linked glycans, most of which essential for EBV life cycle. EBV gp350/220 is also a primary target for neutralizing antibodies in the human hosts and a promising candidate for an EBV vaccine. Here we showed that recombinant GalNAc transferases can glycosylate scan peptides of the EBV gp350/220 envelope protein immobilized on microarray glass slides. We also identified serum IgG antibodies to a selection of peptides and O-glycopeptides, whereas sera from EBV-IgG negative individuals remained negative. We here describe novel glycopeptide epitopes present within immunodominant stretches of EBV gp350/220 and demonstrate a remarkable variability between individual samples with respect to their reactivity patterns to peptides and glycopeptides. The study provides additional insights into the complex B-cell response towards the EBV gp350/220 envelope protein, which may have implications for diagnostic and vaccine developments.
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| 10. |
- Jaaskelainen, A. J., et al.
(författare)
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Performance of a multiplexed serological microarray for the detection of antibodies against central nervous system pathogens
- 2014
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Ingår i: Journal of Microbiological Methods. - : Elsevier BV. - 0167-7012. ; 100, s. 27-31
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Tidskriftsartikel (refereegranskat)abstract
- Central nervous system (CNS) infections have multiple potential causative agents for which simultaneous pathogen screening can provide a useful tool. This study evaluated a multiplexed microarray for the simultaneous detection of antibodies against CNS pathogens. The performance of selected microarray antigens for the detection of IgG antibodies against herpes simplex virus 1 and 2 (HSV-1 and HSV-2), varicella-zoster virus (VZV), adenovirus, Mycoplasma pneumoniae and Borrelia burgdorferi sensu lato, was evaluated using serum sample panels tested with reference assays used in a routine diagnostic laboratory. The microarray sensitivity for HSV-1, HSV-2, VZV, adenovirus and M. pneumonia ranged from 77% to 100%, and the specificity ranged from 74% to 97%. Very variable sensitivities and specificities were found for borrelial antigens of three different VIsE protein IR(6) peptide variants (IR6p1, IR6p2, IR6p4) and three recombinant decorin binding proteins A (DbpA; DbpAla, DbpA91, DbpAG40). For single antigens, good specificity was shown for antigens of IR6p4 and DbpAla (96%), while DbpA91, IR6p1 and IR6p2 were moderately specific (88-92%). The analytical sensitivity of the microarray was dependent on the borrelial IgG concentration of the specimen. The overall performance and technical features of the platform showed that the platform supports both recombinant proteins, whole viruses and peptides as antigens. This study showed diagnostic potential for all six CNS pathogens, including Borrelia burgdorferi sensu lato, using glutaraldehyde based microarray, and further highlighted the importance of careful antigen selection and the requirement for the use of multiple borrelial antigens in order to increase specificity without a major lack of sensitivity. (c) 2014 Elsevier B.V. All rights reserved.
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