| 1. |
- Antonescu, Irina E, et al.
(författare)
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The Permeation of Acamprosate Is Predominantly Caused by Paracellular Diffusion across Caco-2 Cell Monolayers : A Paracellular Modeling Approach
- 2019
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Ingår i: Molecular Pharmaceutics. - : American Chemical Society (ACS). - 1543-8384 .- 1543-8392. ; 16:11, s. 4636-4650
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Tidskriftsartikel (refereegranskat)abstract
- In drug development, estimating fraction absorbed (Fa) in man for permeability-limited compounds is important but challenging. To model Fa of such compounds from apparent permeabilities (Papp) across filter-grown Caco-2 cell monolayers, it is central to elucidate the intestinal permeation mechanism(s) of the compound. The present study aims to refine a computational permeability model to investigate the relative contribution of paracellular and transcellular routes to the Papp across Caco-2 monolayers of the permeability-limited compound acamprosate having a bioavailability of ∼11%. The Papp values of acamprosate and of several paracellular marker molecules were measured. These Papp values were used to refine system-specific parameters of the Caco-2 monolayers, that is, paracellular pore radius, pore capacity, and potential drop. The refined parameters were subsequently used as an input in modeling the permeability (Pmodeled) of the tested compounds using mathematical models collected from two published permeability models. The experimental data show that acamprosate Papp across Caco-2 monolayers is low and similar in both transport directions. The obtained acamprosate Papp, 1.56 ± 0.28 × 10-7 cm·s-1, is similar to the Papp of molecular markers for paracellular permeability, namely, mannitol (2.72 ± 0.24 × 10-7 cm·s-1), lucifer yellow (1.80 ± 0.35 × 10-7 cm·s-1), and fluorescein (2.10 ± 0.28 × 10-7 cm·s-1), and lower than that of atenolol (7.32 ± 0.60 × 10-7 cm·s-1; mean ± SEM, n = 3-6), while the end-point amount of acamprosate internalized by the cell monolayer, Qmonolayer, was lower than that of mannitol. Acamprosate did not influence the barrier function of the monolayers since it altered neither the Papp of the three paracellular markers nor the transepithelial electrical resistance (TEER) of the cell monolayer. The Pmodeled for all the paracellular markers and acamprosate was dominated by the Ppara component and matched the experimentally obtained Papp. Furthermore, acamprosate did not inhibit the uptake of probe substrates for solute carriers PEPT1, TAUT, PAT1, EAAT1, B0,+AT/rBAT, OATP2B1, and ASBT expressed in Caco-2 cells. Thus, the Pmodeled estimated well Ppara, and the paracellular route appears to be the predominant mechanism for acamprosate Papp across Caco-2 monolayers, while the alternative transcellular routes, mediated by passive diffusion or carriers, are suggested to only play insignificant roles.
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| 3. |
- Björk, Ann Kristin, et al.
(författare)
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The reactivity of the back revisited. Are there differences in reactivity in different parts of the back?
- 2017
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Ingår i: Contact Dermatitis. - : Wiley. - 0105-1873. ; 76:1, s. 19-26
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Tidskriftsartikel (refereegranskat)abstract
- Background: In the contact dermatitis literature, it is regularly stated that the patch test reactivity on various areas of the back differs; this might have a large impact on the reproducibility of patch testing. Objectives: To investigate the reproducibility of patch testing on the upper back with regard to the left as opposed to the right side and the medial as opposed to the lateral part of the upper back. The reproducibility over time and with regard to the reactivity pattern was also investigated. Methods: Thirty-one subjects with contact allergy to the metals gold (n=19) or nickel (n=12) were patch tested with serial dilutions, in triplicate applications, on different locations on the upper back. The Friedman test was used for statistical calculations. Results: No significant differences in the reactivity of the back were found. In all gold-allergic patients and 11 of 12 nickel-allergic patients, the allergy could be reproduced with regard to previous patch testing, but the degree of reactivity differed. Conclusions: When a high level of standardization of the patch test technique with the same test system was used, there were no differences in patch test reactions and sites of application on the upper back.
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| 4. |
- Dohoo, Ian R., et al.
(författare)
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Multiple imputation in veterinary epidemiological studies : A case study and simulation
- 2016
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Ingår i: Preventive Veterinary Medicine. - : Elsevier BV. - 0167-5877 .- 1873-1716. ; 129, s. 35-47
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Tidskriftsartikel (refereegranskat)abstract
- The problem of missing data occurs frequently in veterinary epidemiological studies. Most studies use a complete case (CC) analysis which excludes all observations for which any relevant variable have missing values. Alternative approaches (most notably multiple imputation (MI)) which avoid the exclusion of observations with missing values are now widely available but have been used very little in veterinary epidemiology. This paper uses a case study based on research into dairy producers' attitudes toward mastitis control procedures, combined with two simulation studies to evaluate the use of MI and compare results with a CC analysis. MI analysis of the original data produced results which had relatively minor differences from the CC analysis. However, most of the missing data in the original data set were in the dependent variable and a subsequent simulation study based on the observed missing data pattern and 1000 simulations showed that an MI analysis would not be expected to offer any advantages over a CC analysis in this situation. This was true regardless of the missing data mechanism (MCAR - missing completely at random, MAR - missing at random, or NMAR - not missing at random) underlying the missing values. Surprisingly, recent textbooks dealing with MI make little reference to this limitation of MI for dealing with missing values in the dependent variable. An additional simulation study (1000 runs for each of the three missing data mechanisms) compared MI and CC analyses for data in which varying levels (n = 7) of missing data were created in predictor variables. This study showed that MI analyses generally produced results that were less biased on average, were more precise (smaller SEs), were more consistent (less variability between simulation runs) and consequently were more likely to produce estimates that were close to the "truth" (results obtained from a data set with no missing values). While the benefit of MI varied with the mechanism used to generate the missing data, MI always performed as well as, or better than, CC analysis.
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| 7. |
- Nielsen, Christel, et al.
(författare)
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Secular trends in sickness absence among Swedish patients with ankylosing spondylitis and psoriatic arthritis
- 2018
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Ingår i: Rheumatology International. - : Springer Science and Business Media LLC. - 0172-8172 .- 1437-160X. ; 38:2, s. 275-282
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Tidskriftsartikel (refereegranskat)abstract
- The aim was to investigate whether secular trends in sickness absence (SA) were present in patients with ankylosing spondylitis (AS) and psoriatic arthritis (PsA) receiving their diagnosis between 2002 and 2011. A repeated cross-sectional study design was used. Patients were identified in the Skane Healthcare Register (SHR). A washout period of 18 months was applied. The general population seeking health care was used as a reference cohort. SA data from 2003 to 2012 were obtained from the Swedish Social Insurance Agency and converted into net days of SA per year. Within diagnosis and sex, the average number of net days of SA during the calendar year following diagnosis was calculated and plotted against calendar year together with the corresponding SA of the age-standardized reference population. Linear regression on aggregated data, within diagnosis and sex, was applied to formally investigate differences in secular trends among patients and referents. There were 3173 patients and 992,502 referents. Among men diagnosed with AS, the average amount of SA declined by 8.1 net days per year in patients as compared with 2.4 in the referents (p = 0.01). Among PsA patients, the average amount of SA declined by 11.7 net days per year in women as compared with 2.7 in the referents (p < 0.001) and by 7.6 net days per year in men as compared with 1.9 in the referents (p < 0.001). Secular trends of declining SA were present among AS and PsA patients. Trends were also present among the referents, although not at all of the same magnitude.
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| 9. |
- Sterner, Therese, et al.
(författare)
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The Southern Sweden Adolescent Allergy-Cohort : Prevalence of allergic diseases and cross-sectional associations with individual and social factors
- 2019
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Ingår i: Journal of Asthma. - : Informa UK Limited. - 0277-0903 .- 1532-4303. ; 56:3, s. 227-235
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: Asthma and allergic diseases are the most frequent chronic diseases in childhood worldwide, and considered a burden for the affected children and their families. The diseases impose an economic burden on society if not diagnosed and treated properly and management of and these diseases are challenging for healthcare professionals. The aim of the present investigation was to assess the prevalence of allergic diseases in an unselected cohort of adolescents in southern Sweden. Additionally, associations with sociodemographic factors were investigated, as well as impact on daily life. Methods: This cross-sectional study was based on a cohort of n = 1 530 school children, aged 13 to 14, from 13 municipalities in southern Sweden. Data were collected through web-based questionnaires. Results: Of all children 32% reported at least one allergic disease. 67% reported one allergic disease and 33% reported more than one. No allergy-related disease were reported by 68%. Current asthma was reported by 9.8% and current rhino-conjunctivitis was reported by 13%. The prevalence of food hypersensitivity was 12% and the prevalence of eczema was 11%. One to three wheezing attacks were reported from 55% and 40% reported more than four attacks of wheezing in the preceding year. The self-reported allergic diseases were diagnosed by a doctor in; 36% (food hypersensitivity) to 69% (rhinoconjunctivitis) of the cases. Conclusions: A high number of affected children were identified. Some children being undiagnosed and some not receiving satisfactory treatment. These results suggest that additional studies to evaluate treatment procedures in order to improve healthcare for allergic children are warranted.
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| 10. |
- Wilczek, Michael L., et al.
(författare)
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Mammography and Osteoporosis Screening-Clinical Risk Factors and Their Association With Digital X-Ray Radiogrammetry Bone Mineral Density
- 2015
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Ingår i: Journal of clinical densitometry. - : Elsevier. - 1094-6950 .- 1559-0747. ; 18:1, s. 22-29
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to study the association between digital X-ray radiogrammetry (DXR) T-score and clinical risk factors for osteoporosis. Women were recruited 2 d per wk at a single mammography screening center between year 2010 and 2012. Included women answered a questionnaire about risk factors for osteoporosis, and a radiograph of the nondominant hand was obtained for DXR analysis. Univariate associations between DXR T-score and risk factors were examined. A generalized linear regression model was fitted to independent variables with univariate associations at p less than 0.05. The multivariable model was reduced through manual backward elimination, with p greater than 0.1 as the exclusion criterion. Seventy-six percent of the women chose to participate in the study (n = 8810). The difference in number of daily mammograms performed on study vs nonstudy days was not significant. All univariate associations between DXR T-score and potential risk factors were highly significant. The multivariable model included height, weight, age, right-handedness, menopause before age 45, alcohol consumption, cortisone treatment, rheumatic disease, and age x smoking status. The coefficient of determination of the model was 0.37. The association between risk factors for osteoporosis and DXR T-score is similar to previously reported associations with dual-energy X-ray absorptiometry.
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