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Sökning: WFRF:(Svensson Olof) > (2005-2009)

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  • Mukonzo, K, et al. (författare)
  • A novel polymorphism in ABCB1 gene, CYP2B6*6 and sex predict single-dose efavirenz population pharmacokinetics in Ugandans.
  • 2009
  • Ingår i: British journal of clinical pharmacology. - 1365-2125. ; 68:5, s. 690-9
  • Tidskriftsartikel (refereegranskat)abstract
    • center dot Efavirenz is metabolized by highly polymorphic enzymes, CYP2B6 and CYP3A. The effect of the different variant alleles on efavirenz population pharmacokinetics has not yet been fully explored. center dot CYP2B6*6 influences efavirenz steady-state pharmacokinetics. Together with sex it explains 11% of the between-subject variability in apparent oral clearance, but predictions could potentially be improved if additional alleles causing reduced drug metabolism were identified. center dot ABCB1 (3435C -> T) may have effect on efavirenz single-dose and steady-state pharmacokinetics. WHAT THIS STUDY ADDS center dot A new polymorphism in ABCB1 gene (rs3842) and CYP2B6*11 in addition to sex and CYP2B6*6 genotype predict efavirenz single-dose pharmacokinetics. center dot A combined population pharmacogenetic/pharmacokinetic modelling approach allows determination and simulation of determinant factors for efavirenz single-dose pharmacokinetics based on data on gender, biochemical variables and genetic factors in relevant genes (a total of 30 SNPs in CYP2B6, ABCB1 and CYP3A4 genes) in Ugandan population. AIMS Efavirenz exhibits pharmacokinetic variability causing varied clinical response. The aim was to develop an integrated population pharmacokinetic/pharmacogenetic model and investigate the impact of genetic variations, sex, demographic and biochemical variables on single-dose efavirenz pharmacokinetics among Ugandan subjects, using nonmem. METHODS Efavirenz plasma concentrations (n = 402) from 121 healthy subjects were quantified by high-performance liquid chromatography. Subjects were genotyped for 30 single nucleotide polymorphisms (SNPs), of which six were novel SNPs in CYP2B6, CYP3A5 and ABCB1. The efavirenz pharmacokinetics was described by a two-compartment model with zero- followed by first-order absorption. RESULTS Apparent oral clearance (95% confidence interval) was 4 l h l-1 (3.5, 4.5) in extensive metabolizers. In the final model, incorporating multiple covariates, statistical significance was found only for CYP2B6*6 and CYP2B6*11 on apparent oral clearance as well as ABCB1 (rs3842) on the relative bioavailability. Subjects homozygous for CYP2B6*6 (G516T, A785G) and *11 displayed 21 and 20% lower apparent oral clearance, respectively. Efavirenz relative bioavailability was 26% higher in subjects homozygous for ABCB1 (rs3842). The apparent peripheral volume of distribution was twofold higher in women compared with men. CONCLUSIONS The model identified the four factors CYP2B6*6, CYP2B6*11, a novel variant allele in ABCB1 (rs3842) and sex as major predictors of efavirenz plasma exposure in a healthy Ugandan population after single-dose administration. Use of mixed-effects modelling allowed the analysis and integration of multiple pharmacogenetic and demographic covariates in a pharmacokinetic population model.
  • Looi Chee Leong, Jeffrey, et al. (författare)
  • Caudate nucleus volumes in frontotemporal lobar degeneration : differential atrophy in subtypes
  • 2008
  • Ingår i: American Journal of Neuroradiology. - 0195-6108 .- 1936-959X. ; 29:8, s. 1537-1543
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND AND PURPOSE: Frontostriatal circuits involving the caudate nucleus have been implicated in frontotemporal lobar degeneration (FTLD). We assessed caudate nucleus volumetrics in FTLD and subtypes: frontotemporal dementia (FTD, n = 12), semantic dementia (SD, n = 13), and progressive nonfluent aphasia (PNFA, n = 9) in comparison with healthy controls (n = 27) and subjects with Alzheimer disease (AD, n = 19).MATERIALS AND METHODS: Diagnoses were based on accepted clinical criteria. Manual volume measurement of the head and body of the caudate, excluding the tail, was conducted on T1-weighted brain MR imaging scans, using a published protocol, by a single analyst blinded to the diagnosis.RESULTS: Paired t tests (P < .05) showed that the right caudate nucleus volume was significantly larger than the left in controls and PNFA. No hemispheric asymmetry was found in AD, ETD, and SD. Across the groups, there was a positive partial correlation between the left caudate nucleus volume and Mini-Mental State Examination (MMSE) scores (r = 0.393, n = 76, P = .001) with higher left caudate volumes associated with higher MMSE scores. Multivariate analysis of covariance was used to assess the statistical significance between the subject groups (AD, ETD, SD, PNFA, and controls) as independent variables and raw right/left caudate volumes at the within-subject level (covariates: age and intracranial volume; P < .05). Control volume was largest, followed by AD (93% of control volume), SD (92%), PNFA (79%), and ETD (75%).CONCLUSIONS: Volume of the head and body of the caudate nucleus differs in subtypes of FTLD, due to differential frontostriatal dysfunction in subtypes being reflected in structural change in the caudate, and is correlated with cognition
  • Svensson, Marie, et al. (författare)
  • Osmotic stability of the cell membrane of Escherichia coli from a temperature-limited fed-batch process
  • 2005
  • Ingår i: Applied Microbiology and Biotechnology. - 0175-7598 .- 1432-0614. ; 67:3, s. 345-350
  • Tidskriftsartikel (refereegranskat)abstract
    • The temperature-limited fed-batch (TLFB) process is a technique where the oxygen consumption rate is controlled by a gradually declining temperature profile rather than a growth-limiting glucose-feeding profile. In Escherichia coli cultures, it has been proven to prevent an extensive release of endotoxins, i.e. lipopolysaccharides, that occurs in the glucose-limited fed-batch (GLFB) processes at specific growth rates below 0.1 h(-1). The TLFB and the GLFB process were compared to each other when applied to produce the periplasmic, constitutively expressed, enzyme beta-lactamase. The extraction of the enzyme was performed by osmotic shock. A higher production of beta-lactamase was achieved with the TLFB technique while no difference in the endotoxin release was found during the extraction procedure. Furthermore, it was found that growth at declining temperature, generated by the TLFB technique, gradually stabilizes the cytoplasmic membrane, resulting in a significantly increased product quality in the extract from the TLFB cultures in the osmotic shock treatment.
  • Albin, Björn, et al. (författare)
  • Situation for carers of the elderly in Sweden
  • 2008
  • Ingår i: Studies of Community Welfare: Chiiki Fukushi Kenkyu. - Nihon Seimei Saiseikai Osaka. ; :38, s. 72-83
  • Tidskriftsartikel (refereegranskat)abstract
    • In most societies informal care of the elderly (often given by a relative) plays an important role, this article describes the situation and support for carers that exist in Sweden. The description is partly based on the results from the evaluation of a project (“Anhörig 300”) aimed to develop support for carers in the County of Kronoberg as well as from information and documents. Four different typical situations for carers are identified and is an indication of how different situations for carers can be. In the future the support for carers must be paid attention to and further developed. The National Development Plan for the Nursing and Care for elderly in Sweden suggest increased support for carers as a supplement to the public sector elderly care. It is important to involve voluntary organizations to break isolation and loneliness among carers.
  • Berggren, Magnus, et al. (författare)
  • PEDOT : PSS-Based Electrochemical Transistors for Ion-to-Electron Transduction and Sensor Signal Amplification
  • 2008
  • Ingår i: Organic Semiconductors in Sensor Applications. - Springer. - 978-3-540-76314-7 - 978-3-540-76313-0 - 978-3-642-09517-7 ; s. 263-280
  • Bokkapitel (övrigt vetenskapligt)abstract
    • The chapter reports the use of organic electrochemical transistors in sensor applications. These transistors are excellent ion-to-electron transducers and can serve as very sensitive transducers in amperometric sensor applications. To further improve their sensitivity, we outline various amplification circuits all realized in organic electrochemical transistors.
  • Borgström, Fredrik, et al. (författare)
  • Costs and quality of life associated with osteoporosis-related fractures in Sweden
  • 2006
  • Ingår i: Osteoporosis International. - Springer. - 1433-2965. ; 17:5, s. 637-650
  • Tidskriftsartikel (refereegranskat)abstract
    • This prospective observational data collection study assessed the cost and quality of life related to hip, vertebral and wrist fracture 1 year after the fracture, based on a patient sample consisting of 635 male and female patients surviving a year after fracture. Data regarding resource use and quality of life related to fractures was collected by questionnaires at baseline, 4 months and 12 months. Information was collected by the use of patients' records, register sources and by asking the patient. Quality of life was estimated with the EQ-5D questionnaire. Costs were estimated from a societal perspective, including direct and indirect costs. The mean fracture-related cost the year after a hip, vertebral and wrist fracture were estimated, in euros (E), at E14,221, E12,544 and E2,147, respectively [ converted from Swedish krona (SEK) at an exchange rate of 9.1268 SEK/E]. The mean reduction in quality of life was estimated at 0.17, 0.26 and 0.06 for hip, vertebral and wrist fracture, respectively. Based on the results, the yearly burden of osteoporosis in Sweden could be estimated at E0.5 billion (SEK 4.6 billion). The patient sample for vertebral fracture was fairly small and included a high proportion of fractures leading to hospitalization, but they indicate a higher cost and loss of quality of life related to vertebral fracture than previously perceived.
  • Boström, Pontus, 1982-, et al. (författare)
  • Hypoxia converts human macrophages into triglyceride-loaded foam cells.
  • 2006
  • Ingår i: Arteriosclerosis, thrombosis, and vascular biology. - 1524-4636. ; 26:8, s. 1871-6
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: Atherosclerotic lesions have regions that are hypoxic. Because the lesion contains macrophages that are loaded with lipid, we investigated whether hypoxia can influence the accumulation of lipids in these cells. METHODS AND RESULTS: Exposure of human macrophages to hypoxia for 24 hours resulted in an increased formation of cytosolic lipid droplets and an increased accumulation of triglycerides. Exposure of the macrophages to oxidized low-density lipoprotein (oxLDL) increased the accumulation of cytosolic lipid droplets because of an increase in cellular cholesterol esters. The accumulation of lipid droplets in oxLDL-treated cells was further increased after hypoxia, caused by an increased level of triglycerides. Expression analyses combined with immunoblot or RT-PCR demonstrated that hypoxia increased the expression of several genes that could promote the accumulation of lipid droplets. Hypoxia increased the mRNA and protein levels of adipocyte differentiation-related protein (ADRP). It is well known that an increased expression of ADRP increases the formation of lipid droplets. Hypoxia decreased the expression of enzymes involved in beta-oxidation (acyl-coenzyme A synthetase and acyl-coenzyme A dehydrogenase) and increased the expression of stearoyl-coenzyme A desaturase, an important enzyme in the fatty acid biosynthesis. Moreover, exposure to hypoxia decreased the rate of beta-oxidation, whereas the accumulation of triglycerides increased. CONCLUSIONS: The results demonstrate that exposure of human macrophages to hypoxia causes an accumulation of triglyceride-containing cytosolic lipid droplets. This indicates that the hypoxia present in atherosclerotic lesions can contribute to the formation of the lipid-loaded macrophages that characterize the lesion and to the accumulation of triglycerides in such lesions.
  • Carlsson, Beatrice, et al. (författare)
  • Quasispecies dynamics and molecular evolution of human norovirus capsid P region during chronic infection
  • 2009
  • Ingår i: Journal of General Virology. - 0022-1317. ; 90, s. 432-441
  • Tidskriftsartikel (refereegranskat)abstract
    • In this novel study, we have for the first time identified evolutionarily conserved capsid residues in an individual chronically infected with norovirus (GGII.3). From 2000 to 2003, a total of 147 P1-1 and P2 capsid sequences were sequenced and investigated for evolutionarily conserved and functionally important residues by the evolutionary trace (ET) algorithm. The ET algorithm revealed more absolutely conserved residues (ACR) in the P1-1 domain (47/53, 88 %) as compared with the P2 domain (86/133, 64 %). The capsid P1-1 and P2 domains evolved in time-dependent manner, with a distinct break point observed between autumn/winter of year 2000 (isolates P1, P3 and P5) and spring to autumn of year 2001 (isolates P11, P13 and P15), which presumably coincided with a change of clinical symptoms. Furthermore, the ET analysis revealed a similar receptor-binding pattern as reported for Norwalk and VA387 strains, with the CS-4 and CS-5 patch (Norwalk strain) including residues 329 and 377 and residues 306 and 310, respectively, all being ACR in all partitions. Most interesting was that residues 343, 344, 345, 374, 390 and 391 of the proposed receptor A and B trisaccharide binding site (VA387 strain) within the P2 domain remained ACR in all partitions, presumably because there was no selective advantage to alter the histo blood group antigens (HBGA) receptor binding specificity. In conclusion, this study provides novel insights to the evolutionary process of norovirus during chronic infection.
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