| 1. |
- Aspenström-Fagerlund, Bitte, et al.
(author)
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Fatty acids increase paracellular absorption of aluminium across Caco-2 cell monolayers
- 2009
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In: Chemico-Biological Interactions. - : Elsevier BV. - 0009-2797 .- 1872-7786. ; 181:2, s. 272-278
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Journal article (peer-reviewed)abstract
- Passive paracellular absorption, regulated by tight junctions (TJs), is the main route for absorption of poorly absorbed hydrophilic substances. Surface active substances, such as fatty acids, may enhance absorption of these substances by affecting the integrity of TJ and increasing the permeability. It has been suggested that aluminium (Al) absorption occurs mainly by the paracellular route. Herein, we investigated if physiologically relevant exposures of fully differentiated Caco-2 cell monolayers to oleic acid and docosahexaenoic acid (DHA), which are fatty acids common in food, increase absorption of Al and the paracellular marker mannitol. In an Al toxicity test, mannitol and Al absorption through Caco-2 cell monolayers were similarly modulated by Al concentrations between 1 and 30mM, suggesting that absorption of the two compounds occurred via the same pathways. Exposure of Caco-2 cell monolayers to non-toxic concentrations of Al (2mM) and (14)C-mannitol in fatty acid emulsions (15 and 30mM oleic acid, 5 and 10mM DHA) caused a decreased transepithelial electrical resistance (TEER). Concomitantly, fractional absorption of Al and mannitol, expressed as percentage of apical Al and mannitol retrieved at the basolateral side, increased with increasing dose of fatty acids. Transmission electron microscopy was applied to assess the effect of oleic acid on the morphology of TJ. It was shown that oleic acid caused a less structured morphology of TJ in Caco-2 cell monolayers. Taken together our findings indicate that fatty acids common in food increase the paracellular intestinal absorption of Al. These findings may influence future risk assessment of human Al exposure.
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| 2. |
- Aspenström-Fagerlund, Bitte, et al.
(author)
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Oleic acid and docosahexaenoic acid cause an increase in the paracellular absorption of hydrophilic compounds in an experimental model of human absorptive enterocytes
- 2007
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In: Toxicology. - : Elsevier BV. - 0300-483X .- 1879-3185. ; 237:1-3, s. 12-23
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Journal article (peer-reviewed)abstract
- Surface active compounds present in food possibly have the ability to enhance the absorption of water soluble toxic agents. Therefore, we investigated whether fatty acids such as oleic acid and docosahexaenoic acid (DHA), both commonly present in food, negatively affect the integrity of tight junctions (TJ) in the intestinal epithelium and thereby increase the absorption of poorly absorbed hydrophilic substances. Caco-2 cells, which are derived from human absorptive enterocytes, were grown on permeable filters for 20-25 days. Differentiated cell monolayers were apically exposed for 90min to mannitol in emulsions of oleic acid (5, 15 or 30mM) or DHA (5, 15 or 30mM) in an experimental medium with or without Ca(2+) and Mg(2+). Absorption of (14)C-mannitol increased and trans-epithelial electrical resistance (TEER) decreased in cell monolayers exposed to oleic acid and DHA, compared to controls. Cytotoxicity, measured as leakage of LDH, was higher in groups exposed to 30mM oleic acid and all concentrations of DHA. Morphology of the cell monolayers was studied by using fluorescence microscopy. Exposure of cell monolayers to 5mM DHA for 90min resulted in a profound alteration of the cell-cell contacts as detected by staining the cells for beta-catenin. Oleic acid (30mM) treatment also induced dissolution of the cell-cell contacts but the effect was not as pronounced as with DHA. Cell monolayers were also exposed for 180min to 250nM cadmium (Cd) in emulsions of oleic acid (5 or 30mM) or DHA (1 or 5mM), in an experimental medium with Ca(2+) and Mg(2+). Retention of Cd in Caco-2 cells was higher after exposure to 5mM oleic acid but lower after exposure to 30mM oleic acid and DHA. Absorption of Cd through the monolayers increased after DHA exposure but not after exposure to oleic acid. Our results indicate that fatty acids may compromise the integrity of the intestinal epithelium and that certain lipids in food may enhance the paracellular absorption of poorly absorbed hydrophilic substances.
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| 3. |
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| 4. |
- Aspenström-Fagerlund, Bitte, et al.
(author)
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Oleic acid decreases BCRP mediated efflux of mitoxantrone in Caco-2 cell monolayers
- 2012
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In: Food and Chemical Toxicology. - : Elsevier BV. - 0278-6915 .- 1873-6351. ; 50:10, s. 3635-3645
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Journal article (peer-reviewed)abstract
- Breast cancer resistance protein (BCRP) efflux restricts intestinal absorption of substances like heterocyclic amines, mycotoxins and certain human and veterinary drugs. Fat rich meals seem to increase absorption of drugs which are BCRP substrates or inhibitors. We therefore hypothesize that absorption of toxicants normally effluxed by BCRP are increased by fatty acids in food. Transport across and accumulation of H-3-Mitoxantrone (MXR) in Caco-2 cell monolayers were measured after 60 min exposure to emulsions of H-3-MXR (1 mu M) and oleic acid (0.5-5 mM). In addition, BCRP gene expression (RT-PCR) and the amount of BCRP protein (Western blot) were measured in oleic acid exposed Caco-2 cells. Oleic acid increased transport of MXR in a concentration dependent manner and 2 mM oleic acid or higher increased accumulation of MXR in cells, without any signs of cytotoxicity. Gene expression of BCRP was increased after exposure to oleic acid for 6 h, but the amount of BCRP protein was not increased. In conclusion, oleic acid clearly induced BCRP gene expression and reduced BCRP mediated efflux, although the amount of BCRP in cells was not affected. Consequently, effects of fatty acids on BCRP mediated efflux are important to consider in risk assessment of toxicants in food.
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| 5. |
- Aspenström-Fagerlund, Bitte, et al.
(author)
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Oleic acid increases intestinal absorption of the BCRP/ABCG2 substrate, mitoxantrone, in mice
- 2015
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In: Toxicology Letters. - : Elsevier BV. - 0378-4274 .- 1879-3169. ; 237:2, s. 133-139
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Journal article (peer-reviewed)abstract
- The efflux transporter breast cancer resistance protein (BCRP/ABCG2) decrease intestinal absorption of many food toxicants. Oleic acid increases absorption of the specific BCRP substrate mitoxantrone (MXR), and also BCRP gene expression in human intestinal Caco-2 cells, suggesting that oleic acid affect the BCRP function. Here, we investigated the effect of oleic acid on intestinal absorption of MXR in mice. Mice were orally dosed with 2.4 g oleic acid/kg b.w. and 1 mg MXR/kg b.w., and sacrificed 30, 60, 90 or 120 min after exposure, or were exposed to 0.6, 2.4 or 4.8 g oleic acid/kg b.w. and 1mg MXR/kg b.w., and sacrificed 90 min after exposure. Mice were also treated with Ko143 together with MXR and sacrificed after 60 min, as a positive control of BCRP-mediated effects on MXR absorption. Absorption of MXR increased after exposure to oleic acid at all doses, and also after exposure to Ko143. Intestinal BCRP gene expression tended to increase 120 min after oleic acid exposure. Our results in mice demonstrate that oleic acid decreases BCRP-mediated efflux, causing increased intestinal MXR absorption in mice. These findings may have implications in humans, concomitantly exposed to oleic acid and food contaminants that, similarly as MXR, are substrates of BCRP.
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| 6. |
- Fagerlund, Anders, et al.
(author)
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Gynecomastia: A systematic review.
- 2015
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In: Journal of plastic surgery and hand surgery. - 2000-6764. ; 49:6, s. 311-318
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Research review (peer-reviewed)abstract
- Gynecomastia is a common medical problem presenting in nearly a third of the male population. Treatment for gynecomastia can be either pharmacological or surgical. Patients with gynecomastia often experience affected quality-of-life. The aim of this systematic review was to analyze the quality of evidence of the current literature in relation to different treatment modalities and Quality-of-Life in patients with gynecomastia.
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| 7. |
- Fagerlund, Anders, et al.
(author)
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Gynecomastia in Patients with Prostate Cancer: A Systematic Review.
- 2015
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In: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 10:8
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Journal article (peer-reviewed)abstract
- Gynecomastia and/or mastodynia is a common medical problem in patients receiving antiandrogen (bicalutamide or flutamide) treatment for prostate cancer; up to 70% of these patients result to be affected; furthermore, this can jeopardise patients' quality of life.
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| 8. |
- Hedenström, Anders, et al.
(author)
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Magnetic resonance imaging versus chemical fat extraction in a small passerine, the willow warbler Phylloscopus trochilus: A fat-score based statistical comparison
- 2009
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In: Journal of Avian Biology. - 0908-8857. ; 40:4, s. 457-460
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Journal article (peer-reviewed)abstract
- Abstract in UndeterminedThe amount of fat of a bird is a fundamental metric commonly used by avian biologists in studies of migration, winter energy management and condition. The methods used for estimating fat content range from simply measuring body mass and subtracting the estimated lean mass, visual scoring of subcutaneous fat deposits, to destructive extraction using a Soxhlet apparatus. We used magnetic resonance imaging (MRI) for non-invasive estimation of fat content in willow warblers Phylloscopus trochilus. According to an indirect comparison, made using a standardized fat scoring system as a common measure, the MRI method gave very similar fat amount as Soxhlet extraction and we discuss advantages of using MRI over alternative methods. It was also shown that the commonly used fat scoring system yielded a nonlinear relationship between fat mass and fat score.
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| 9. |
- Hytter, Anders, 1954-, et al.
(author)
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Destructive Managerial Behavior and Employee Health
- 2009
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In: Paper presented at the conference Work, Stress and Health 2009: Global Concerns and Approaces, in San Juan, Puerto Rico.
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Conference paper (other academic/artistic)
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| 10. |
- Hytter, Anders, et al.
(author)
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Destruktiva chefsbeteenden och medarbetarhälsa
- 2010
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In: Ledning och organisering av proffessionsstarka verksamheter. - Växjö : Linnéuniversitetet, institutionen för samhällsvetenskaper. - 9789186491543 ; , s. 75-97
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Book chapter (peer-reviewed)
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| 11. |
- Kazamia, Kalliopi, et al.
(author)
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Children with juvenile idiopathic arthritis frequently experience interruptions to their medical therapy
- 2014
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In: Acta Paediatrica. - : Wiley. - 0803-5253 .- 1651-2227. ; 103:5, s. 529-536
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Journal article (peer-reviewed)abstract
- AimTo study real-life experiences of drug treatment discontinuations and safety in a well-defined cohort of patients with juvenile idiopathic arthritis (JIA), over an eleven-year period in Uppsala County, Sweden. MethodsClinical charts of all incident and prevalent cases of juvenile arthritis were reviewed prospectively by an experienced paediatric rheumatologist. Each patient file was supplemented retrospectively regarding hereditary diseases, clinical data and aspects of pharmacological treatment. ResultsSevere adverse events from methotrexate or biological agents were rare, but 84 occasions of interrupted therapy due to adverse events or inefficacy were identified within 225 treatment periods (37.3%) in the 156 patients (108 girls and 48 boys) studied. The median observation period was 8.6years after disease onset (minimum 1.33, maximum 17.5years). Oral and subcutaneous methotrexate caused adverse events in 22.6% of the treatment periods and biological agents in 19.2% (p=0.71). Discontinuation of treatment periods was equally common for methotrexate (38.7%) and biological agents (33.3%) (p=0.53). ConclusionOur study shows a high percentage of interrupted medical therapies, due to adverse events or inefficacy, in children with JIA. Adverse events from methotrexate and biological agents were seldom severe. The results highlight the need for better predictive factors to guide therapy.
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| 12. |
- Lundkvist, B, et al.
(author)
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Cerebrospinal fluid hydrodynamics after placement of a shunt with an antisiphon device : a long-term study.
- 2001
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In: Journal of Neurosurgery. - : Journal of Neurosurgery Publishing Group (JNSPG). - 0022-3085 .- 1933-0693. ; 94:5, s. 750-6
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Journal article (peer-reviewed)abstract
- OBJECT: Few studies have been performed to investigate the cerebrospinal fluid (CSF) hydrodynamic profile in patients with idiopathic adult hydrocephalus syndrome (IAHS) before and after shunt implantation. The authors compared the in vivo CSF hydrodynamic properties, including the degree of gravity-induced CSF flow, of a shunt with an antisiphon device with a standard shunt.METHODS: Twelve patients with IAHS underwent insertion of shunts with Delta valves. Clinical testing, magnetic resonance imaging, and CSF hydrodynamic investigations were conducted with intracranial pressure (ICP), gravity effect, and pressure-flow curve of the shunt estimated at baseline and at 3 and 12 months postoperatively. No shunt was revised. Despite postoperative clinical improvement in all patients who received Delta valves, the mean ICP was only moderately reduced (mean decrease at 3 months 0.3 kPa [p = 0.02], at 12 months 0.2 kPa [not significant]). Patients with the greatest increase in ICP preoperatively had the most pronounced decrease postoperatively. The hydrostatic effect of the Delta valves was significantly lower than with the Hakim shunts (0.1-0.2 kPa compared with 0.6 kPa). The increased conductance (that is, lowered resistance) was up to 14 times higher with the Delta valves compared with preoperative levels.CONCLUSIONS: The function of a CSF shunt may be more complicated than previously thought; the subcutaneous pressure acting on the antisiphon device can modify the shunt characteristics. A compensatory increase in CSF production may counteract the increased outflow through the shunt. The improved CSF outflow conductance may increase the intracranial compliance and thereby dampen a pathological ICP waveform.
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| 13. |
- Wirestam, Ronnie, et al.
(author)
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MAGNETIC RESONANCE IMAGING FOR NONINVASIVE ANALYSIS OF FAT STORAGE IN MIGRATORY BIRDS
- 2008
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In: The Auk. - 0004-8038. ; 125:4, s. 965-971
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Journal article (peer-reviewed)abstract
- Many bird species migrate long distances without any food intake and must optimize storage of energy with respect to minimization of aerodynamic drag. To contribute to the understanding of this issue, we investigated, by magnetic resonance imaging (MRI), spatial distributions of body fat during the accumulation process before migration. We collected data from 12 Lesser Whitethroats (Sylvia curruca), 9 European Robins (Erithacus rubecula), 8 Blackcaps (Sylvia atricapilla), and 5 Willow Warblers (Phylloscopus trochilus). On average, each bird was examined 3.2 times. Adipose tissue was Visualized using T1-weighted spin-echo MRI at 1.5 T. Fat-containing pixels were identified by an image-segmentation procedure. Data were analyzed with respect to (1) fat distribution within the body, (2) relationship between frontal surface area and fat mass increase, (3) fat mass increase in comparison with increase in total body mass, and (4) fat mass in relation to standardized visual classification of fat deposits. Fat increase was reflected by a larger frontal area, though adipose tissue was not deposited equally along the length of the bird. Slices with largest frontal area showed relatively low fractions of fat. Frontal area increased less than expected from conventional geometrical models, which indicates that the body shape is altered. The increase in total body mass was generally higher than the total fat mass increase, which indicates that other tissue, most likely flight muscle, can metabolize rapidly in correlation with fat accumulation. In Blackcap, total fat mass was not linearly related to standardized fat-deposit classes. Received 31 August 2007, accepted 7 June 2008.
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