| 1. |
- Taipalensuu, Jan, et al.
(author)
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Correlation of gene expression of ten drug efflux proteins of the ATP-binding cassette transporter family in normal human jejunum and inhuman intestinal epithelial Caco-2 cell monolayers
- 2001
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In: Journal of Pharmacology and Experimental Therapeutics. - 0022-3565 .- 1521-0103. ; 299:1, s. 164-170
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Journal article (peer-reviewed)abstract
- This investigation describes the expression and interindividual variability in transcript levels of multiple drug efflux systems in the human jejunum and compares the expression profiles in these cells with that of the commonly used Caco-2 cell drug absorption model. Transcript levels of ten-drug efflux proteins of the ATP-binding cassette (ABC) transporter family [MDR1, MDR3, ABCB5, MRP1-6, and breast cancer resistance protein (BCRP)], lung resistance-related protein (LRP), and CYP3A4 were determined using quantitative polymerase chain reaction in jejunal biopsies from 13 healthy human subjects and in Caco-2 cells. All genes except ABCB5 were expressed, and transcript levels varied between individuals only by a factor of 2 to 3. Surprisingly, BCRP and MRP2 transcripts were more abundant in jejunum than MDR1 transcripts. Jejunal transcript levels of the different ABC transporters spanned a range of three log units with the rank order: BCRP approximately MRP2 > MDR1 approximately MRP3 approximately MRP6 approximately MRP5 approximately MRP1 > MRP4 > MDR3. Furthermore, transcript levels of 9 of 10 ABC transporters correlated well between jejunum and Caco-2 cells (r2 = 0.90). However, BCRP exhibited a 100-fold lower transcript level in Caco-2 cells compared with jejunum. Thus, the expression of a number of efflux protein transcripts in jejunum are equal to, or even higher than, that of MDR1, suggesting that the roles of these proteins (in particular BCRP and MRP2) in intestinal drug efflux have been underestimated. Also, we tentatively conclude that the Caco-2 cell line is a useful model of jejunal drug efflux, if the low expression of BCRP is taken into account.
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| 2. |
- Bondesson, Laban, et al.
(author)
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Density functional theory calculations of hydrogen bonding energies of drug molecules
- 2006
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In: Journal of Molecular Structure. - : Elsevier BV. - 0022-2860 .- 1872-8014 .- 0166-1280. ; 776:1-3, s. 61-68
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Journal article (peer-reviewed)abstract
- Hydrogen bonding energies of several drug molecules have been calculated using hybrid density functional theory with inclusion of basis set superposition error corrections. The calculated total hydrogen bonding energy of each drug molecule has been compared with the result of a conceptually simple additive model, from which the summation of hydrogen bonding energies of individual polar groups present in the drug molecule are considered. It is shown that the validity of the additive model is strongly conditional, and to some extent predictable: In cases where the hydrogen bonding group is isolated the addition model can be of relevance, while in cases where the hydrogen bonding groups are interconnected through pi-conjugation rings or chains of the drug molecules it introduces substantial errors. It is suggested that such strong cooperative effects of hydrogen bonds should always be taken into account for evaluation of the hydrogen bonding energies of drug molecules.
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| 3. |
- Bondesson, Laban, et al.
(author)
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Hydrogen bonding effects on infrared and Raman spectra of drug molecules
- 2007
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In: Spectrochimica Acta Part A - Molecular and Biomolecular Spectroscopy. - : Elsevier BV. - 1386-1425 .- 1873-3557. ; 66:2, s. 213-224
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Journal article (peer-reviewed)abstract
- Infrared and Raman spectra of three drug molecules, aspirin, caffeine and ibuprofen, in gas phase and in aqueous solution have been simulated using hybrid density functional theory. The long range solvent effect is modelled by the polarizable continuum model, while the short range hydrogen bonding effects are taken care of by the super-molecular approach with explicit inclusion of water molecules. The calculated spectra are found to compare well with available experimental results. The agreement obtained make grounds for proposing theoretical modeling as a tool for characterizing changes in the bonding environments of drug molecules in terms of particular variations in their IR and Raman spectra.
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| 4. |
- Garberg, Per, et al.
(author)
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Binding of tellurium to hepatocellular selenoproteins during incubationwith inorganic tellurite : consequences for the activity ofselenium-dependent glutathione peroxidase
- 1999
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In: International Journal of Biochemistry and Cell Biology. - 1357-2725 .- 1878-5875. ; 31:2, s. 291-301
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Journal article (peer-reviewed)abstract
- The metallic group XVIa elements selenium and tellurium possess remarkably similar chemical properties. However, unlike selenium, tellurium is not an essential micronutrient and, indeed, induces both acute and chronic toxicity in a variety of species. Despite this, very little is known of the molecular mechanisms of toxicity of tellurium, particularly with respect to potential chemical interactions with selenium-containing components in the cell. In this work we describe a novel interaction of inorganic tellurite with hepatocellular selenoproteins, particularly with selenium-dependent glutathione peroxidase. The accumulation of (121Te)-tellurite into cultured primary rat liver hepatocytes was shown to be much more rapid than that of (75Se)-selenite on a molar basis. Neither the uptake of (121Te)-tellurite nor of (75Se)-selenite was affected by a large molar excess of the unlabelled counterpart, respectively. Interestingly, separation of the hepatocellular proteins on continuous pH denaturing gels demonstrated clear binding of radiolabelled tellurium to a number of protein bands, including one at 23 and one at 58 kDa, which corresponded to proteins readily labelled in cells treated with (75Se)-selenite. The binding of (121Te) to these proteins was insensitive to reduction with mercaptoethanol and not affected by pre-treatment of the cells with cycloheximide. When purified selenium-dependent glutathione peroxidase was treated directly with (121Te)-tellurite, the protein became labelled in an analogous manner to that achieved in intact cells. This was not affected by coincubation of the enzyme with (121Te)-tellurite and one or both of its substrates. Additionally, incubation of the peroxidase with tellurite effectively inhibited its ability to catalyse glutathione-dependent reduction of hydrogen peroxide. These data suggest that inorganic tellurite delivers tellurium to the intracellular milieu in a form capable of binding to some intracellular selenoproteins and at least in the case of glutathione peroxidase, cause inhibition of catalytic activity. The nature of the binding seems not to be due to the insertion of tellurocysteine into the protein and the insensitivity to reductive cleavage with mercaptoethanol seems to preclude the formation of stable telluro-selenides in the proteins. These data may offer alternative explanations for the established toxicity of tellurium via disruption of selenoprotein function, particularly by the induction of intracellular oxidative stress by the inhibition of Se-dependent glutathione peroxidase.
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| 5. |
- Haukø, Anne-Marit, et al.
(author)
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BRAVENT – Veileder for brannteknisk prosjektering av ventilasjonsanlegg i skolebygg
- 2024
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Reports (other academic/artistic)abstract
- Dette dokumentet er en veileder. Veilederen skal benyttes av rådgivende ingeniører i brannteknisk prosjektering av ventilasjonsanlegg i skolebygg. Det fokuseres på rømningssikkerhet og skadebegrensning ved små branner i en tidlig fase av brannforløpet. Veilederen beskriver forutsetninger for bruk, krav og preaksepterte ytelser i VTEK, samt ulike typer ventilasjonsanlegg med tilhørende komponenter. Dokumentet illustrerer typiske prinsippløsninger for ulike ventilasjonsstrategier i bygg, samt forskningsresultater fra brannforsøk og undersøkelser i tidligere faser av BRAVENT-prosjektet. Veilederen tar for seg nybygg, eksisterende bygg og verneverdige bygg hvor grensesnittet mellom rådgivende ingeniør brann (RIBr), ventilasjon (RIV), elektro (RIE) og automasjon (RIAut) defineres. En sjekkliste oppsummerer viktige punkter å hensynta ved prosjektering av ventilasjonsanlegg. Rutiner for drift og vedlikehold beskrives til slutt.
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| 6. |
- Haukø, Anne-Marit, et al.
(author)
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Functional testing of ventilation systems in schools during activated fire alarm - Coherence with the fire safety strategy
- 2022
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In: RISE rapport 2022:72. https://ri.diva-portal.org/smash/get/diva2:1657152/FULLTEXT01.pdf. ; , s. 63-64
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Conference paper (other academic/artistic)abstract
- The purpose of this paper is to present results from functional testing of ventilation systems in schools during activated fire alarm. It was investigated whether the results had coherence with the ventilation strategy in the fire safety concept and the function description for the ventilation system. Functional testing was performed at several schools in three different municipalities in Norway. Results from the preliminary mapping showed that some of the personnel responsible for maintenance of the ventilation systems lacked knowledge about the system's function during fire. Older schools often don't have a fire safety strategy at all, whereas newer schools and renovated schools normally have well documented fire safety strategies, including the ventilation system's function during fire. However, there is little or no information in the building's MOM-documentation (management, operation and maintenance) about how functional testing must be performed. The functional testing showed several incoherencies with the fire safety strategy of the school buildings.
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| 7. |
- Haukø, Anne-Marit, et al.
(author)
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Prosjektnotat : Kontrollplan – Ventilasjonsanleggets funksjon under brann
- 2024
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Reports (other academic/artistic)abstract
- Dette notatet er en delleveranse i arbeidspakke WP3 i prosjektet BRAVENT – Effektiv ventilasjon av røyk fra små branner. Notatet med tilhørende vedlegg Kontrollplan gir en beskrivelse av hvordan periodisk kontroll og daglig/ukentlig internkontroll av ventilasjonsanleggets funksjon under brann i skolebygg kan utføres. Kontrollplanen kan også være nyttig for bruk i andre offentlige formålsbygg.
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