| 1. |
- Artursson, Magnus, et al.
(author)
-
Aspekter på samhällsutveckling
- 2005
-
In: Bronsåldersbygd 2300-500 f. Kr.. - 1650-2787. - 9172093765 ; , s. 496-547
-
Book chapter (other academic/artistic)abstract
- ... Den förändringsprocess som vi här har försökt åskådliggöra är nära knuten till en förändring av ideologi och mentalitet, där den tidigare kollektivt präglade ideologin försvagades och successivt öppnade upp för en ökad stratifiering av samhället. Det finns tydliga tendenser i det arkeologiska materialet mot en ökad betoning och uppvisning av politisk, ekonomisk och militär makt. Denna demonstration av makt når sitt maximum under bronsålderns period II, 1500-1300 f. Kr., då de materiella lämningarna visar att man lagt en stor betydelse vid visuell och rituell uppvisning av hög social position ...
|
|
| 2. |
- Hubatsch, Ina, et al.
(author)
-
Beta- and gamma-di- and tripeptides as potential substrates for the oligopeptide transporter hPepT1
- 2007
-
In: Journal of Medicinal Chemistry. - : American Chemical Society (ACS). - 0022-2623 .- 1520-4804. ; 50:21, s. 5238-5242
-
Journal article (peer-reviewed)abstract
- The hPepT1-mediated transport properties of a series of 11 synthesized beta- and gamma-peptides have been studied in Caco-2 cells. The results show that several of the compounds interact with the peptide transporter, but only two beta-dipeptides act as substrates and are transported across the cell monolayers. These two are less-efficient substrates than alfa-peptides. Larger derivatives than beta-dipeptides do not act as hPepT1 substrates, but instead, they appear to be substrates for P-glycoprotein efflux.
|
|
| 3. |
- Unéus, Lars, 1971-, et al.
(author)
-
Evaluation of on-line flue gas measurements by MISiCFET and metal-oxide sensors in boilers
- 2005
-
In: IEEE Sensors Journal. - 1530-437X .- 1558-1748. ; 5:1, s. 75-81
-
Journal article (peer-reviewed)abstract
- Metal insulator silicon carbide field-effect transistor sensors, metal-oxide sensors, and a linear Lambda sensor in an electronic nose was used to measure on-line in hot flue gases from a boiler. Flue gas from a 100-MW pellets-fuelled boiler has been used to feed the experimental setup. Several reference instruments, which measure the flue gases in parallel to the sensor array, are connected to the electronic nose. Data was collected during six weeks and then evaluated. Using principal component analysis as the data evaluation method, different operating modes for the boiler have been identified in the data set. The different modes could be described in terms of high or low O 2 and CO concentration. Furthermore, we have shown that it seems possible to use a sensor array to determine the operating mode of the boiler and, by partial least-squares models, measure the CO concentration when the boiler operates in its optimum mode.
|
|
| 4. |
- Ahlin, Gustav, 1977-, et al.
(author)
-
Endogenous Gene and Protein Expression of Drug Transporting Proteins in Cell Lines Routinely used in Drug Discovery Programs
- 2009
-
In: Drug Metabolism And Disposition. - : American Society for Pharmacology & Experimental Therapeutics (ASPET). - 0090-9556 .- 1521-009X. ; 37:12, s. 2275-2283
-
Journal article (peer-reviewed)abstract
- The aim of this study was to investigate the gene and protein expression profiles of important drug transporting proteins in human cell lines commonly used for studies of drug transport mechanisms. Human cell lines used to transiently or stably express single transporters (HeLa, HEK293) and leukaemia cell lines used to study drug resistance by ABC-transporters (HL-60, K562) were investigated, and compared with organotypic cell lines (HepG2, Saos-2, Caco-2 and Caco-2 TC7). For gene expression studies, real-time PCR was used, while monospecific polyclonal antibodies were generated and used to investigate protein expression by immunohistochemistry. Thirty-six transporters were studied for gene expression and nine for protein expression. The antibodies were validated using expression patterns in human tissues. Finally, the function of one ubiquitously expressed transporter, MCT1; SLC16A1 was investigated using 14C-lactic acid as a substrate. In general, the adherent cell lines (HeLa, HEK293) displayed low transporter expression and the expression patterns were barely affected by transfection. The leukaemia cell lines (K562, HL-60) and Saos-2 also had low endogenous transporter expression, while the organotypic cell lines (HepG2 and Caco-2) showed higher expression of some transporters. Comparison of gene and protein expression profiles gave poor correlations, but better agreement was obtained for antibodies with a good validation score, indicating that antibody quality was a significant variable. Importantly, the monocarboxylic acid transporting protein MCT1 was significantly expressed in all, and functional in most of the cell lines, indicating that MCT1 may be a confounding factor when the transport of small anionic drugs is investigated.
|
|
| 5. |
- Ahlin, Gustav, 1977-
(author)
-
In vitro and in silico prediction of drug-drug interactions with transport proteins
- 2009
-
Doctoral thesis (other academic/artistic)abstract
- Drug transport across cells and cell membranes in the human body is crucial for the pharmacological effect of drugs. Active transport governed by transport proteins plays an important role in this process. A vast number of transport proteins with a wide tissue distribution have been identified during the last 15 years. Several important examples of their role in drug disposition and drug-drug interactions have been described to date. Investigation of drug-drug interactions at the transport protein level are therefore of increasing interest to the academic, industrial and regulatory research communities. The gene expression of transport proteins involved in drug transport was investigated in the jejunum, liver, kidney and colon to better understand their influence on the ADMET properties of drugs. In addition, the gene and protein expression of transport proteins in cell lines, widely used for predictions of drug transport and metabolism, was examined. The substrate and inhibitor heterogeneity of many transport proteins makes it difficult to foresee whether the transport proteins will cause drug-drug interactions. Therefore, in vitro assays for OCT1 and OATP1B1, among the highest expressed transport proteins in human liver, were developed to allow investigation of the inhibitory patterns of these proteins. These assays were used to investigate two data sets, consisting of 191 and 135 registered drugs and drug-like molecules for the inhibition of OCT1 and OATP1B1, respectively. Numerous new inhibitors of the transport proteins were identified in the data sets and the properties governing inhibition were determined. Further, antidepressant drugs and statins displayed strong inhibition of OCT1 and OATP1B1, respectively. The inhibition data was used to develop predictive in silico models for each of the two transport proteins. The highly polymorphic nature of some transport proteins has been shown to affect drug response and may lead to an increased risk of drug-drug interactions, and therefore, the OCT1 in vitro assay was used to study the effect of common genetic variants of OCT1 on drug inhibition and drug-drug interactions. The results indicated that OCT1 variants with reduced function were more susceptible to inhibition. Further, a drug-drug interaction of potential clinical significance in the genetic OCT1 variant M420del was proposed. In summary, gene expression of transport proteins was investigated in human tissues and cell lines. In vitro assays for two of the highest expressed liver transport proteins were used to identify previously unknown SLC transport protein inhibitors and to develop predictive in silico models, which may detect previously known drug-drug interactions and enable new ones to be identified at the transport protein level. In addition, the effect of genetic variation on inhibition of the OCT1 was investigated.
|
|
| 6. |
- Ahlin, Gustav, et al.
(author)
-
Structural requirements for drug inhibition of the liver specific human organic cation transport protein 1
- 2008
-
In: Journal of Medicinal Chemistry. - : American Chemical Society (ACS). - 0022-2623 .- 1520-4804. ; 51:19, s. 5932-5942
-
Journal article (peer-reviewed)abstract
- The liver-specific organic cation transport protein (OCT1; SLC22A1) transports several cationic drugs including the antidiabetic drug metformin and the anticancer agents oxaliplatin and imatinib. In this study, we explored the chemical space of registered oral drugs with the aim of studying the inhibition pattern of OCT1 and of developing predictive computational models of OCT1 inhibition. In total, 191 structurally diverse compounds were examined in HEK293-OCT1 cells. The assay identified 47 novel inhibitors and confirmed 15 previously known inhibitors. The enrichment of OCT1 inhibitors was seen in several drug classes including antidepressants. High lipophilicity and a positive net charge were found to be the key physicochemical properties for OCT1 inhibition, whereas a high molecular dipole moment and many hydrogen bonds were negatively correlated to OCT1 inhibition. The data were used to generate OPLS-DA models for OCT1 inhibitors; the final model correctly predicted 82% of the inhibitors and 88% of the noninhibitors of the test set.
|
|
| 7. |
- Andersson, Margaretha, et al.
(author)
-
Characterization of Surface-Modified Nanoparticles for in Vivo Biointeraction. A Sedimentation Field Flow Fractionation Study
- 2005
-
In: Analytical Chemistry. ; 77, s. 5488-5493
-
Journal article (peer-reviewed)abstract
- Sedimentation field flow fractionation (SdFFF) is an emerging high-performance analytical tool for separation and determination of size and adsorption characteristics of colloidal particles. This study demonstrates how SdFFF can be used to characterize nanoparticles prepared for in vivo applications including (1) the quantification of polymer uptake on nanoparticles where surface coverage is crucial and (2) the coupling of cell adhesive peptides containing the Arg-Gly-Asp motif (RGD). Quantitative information about polymer adhesion in order to prepare a bioinert surface and an accurate determination of ligand uptake are both of obvious importance for the understanding of, for example, relations between the number of attached molecules for biointeraction and an observed therapeutic effect. In addition, the present work highlights the necessity to perform careful characterization of commercially available particulate starting materials, in terms of size and polydispersity, prior to biological experimentation.
|
|
| 8. |
|
|
| 9. |
- Avdeef, Alex, et al.
(author)
-
Caco-2 permeability of weakly basic drugs predicted with the Double-Sink PAMPA method :
- 2005
-
In: European Journal of Pharmaceutical Sciences. - : Elsevier BV. - 0928-0987. ; 24:4, s. 333-49
-
Journal article (peer-reviewed)abstract
- The aim of this study was to analyze pH-dependent permeability of cationic drugs in Caco-2 cell monolayers using the method and to correlate the results with those obtained in PAMPA (parallel artificial membrane permeability assay). The pH-dependent permeability of verapamil and propranolol was studied in Caco-2 cell monolayers. The data were subsequently processed using software developed for the PAMPA method. Literature values for an additional nine cationic drugs were also analyzed. Double-Sink PAMPA data were also obtained for the same cationic drugs, to compare with the Caco-2 data. The Algorithm Builder program was then used to develop a predictive model of Caco-2 permeability based on PAMPA permeability and calculated Abraham molecular descriptors. From the relationship between permeability and pH it was shown that in PAMPA only the uncharged form of the drugs permeated across the membrane barrier, while charged and ionized forms of the drugs were significantly permeable in Caco-2. The charged-form permeability, Pi, was therefore determined and subsequently subtracted from all permeability coefficients in Caco-2 prior to the comparison with PAMPA. The resulting intrinsic permeability coefficients (Po) obtained in Caco-2 were successfully related to those derived from the PAMPA model. In this study we have shown that permeability coefficients obtained in PAMPA can predict the passive transcellular permeability in Caco-2.
|
|
| 10. |
|
|
