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Sökning: hsv:(MEDICIN OCH HÄLSOVETENSKAP) hsv:(Medicinska och farmaceutiska grundvetenskaper) hsv:(Farmaceutiska vetenskaper) > Örebro universitet

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1.
  • Eriksson, Leif A., 1964-, et al. (författare)
  • Tetrazole derivatives as cytochrome p450 inhibitors
  • 2019
  • Patent (populärvet., debatt m.m.)abstract
    • According to the invention there is provided a compound of formula I, wherein R1 and R2 have meanings given in the description, which compounds are useful in the treatment of skin disorders and other diseases.
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2.
  • Andersson, Sören, 1957-, et al. (författare)
  • CHIMERIC MOMP ANTIGEN
  • 2015
  • Patent (populärvet., debatt m.m.)
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3.
  • Abdurahman, Samir, 1965-, et al. (författare)
  • Activity of the small modified amino acid alpha-hydroxy glycineamide on in vitro and in vivo human immunodeficiency virus type 1 capsid assembly and infectivity
  • 2008
  • Ingår i: Antimicrobial Agents and Chemotherapy. - 0066-4804 .- 1098-6596. ; 52:10, s. 3737-3744
  • Tidskriftsartikel (refereegranskat)abstract
    • Upon maturation of the human immunodeficiency virus type 1 (HIV-1) virion, proteolytic cleavage of the Gag precursor protein by the viral protease is followed by morphological changes of the capsid protein p24, which will ultimately transform the virus core from an immature spherical to a mature conical structure. Virion infectivity is critically dependent on the optimal semistability of the capsid cone structure. We have reported earlier that glycineamide (G-NH(2)), when added to the culture medium of infected cells, inhibits HIV-1 replication and that HIV-1 particles with aberrant core structures were formed. Here we show that it is not G-NH(2) itself but a metabolite thereof, alpha-hydroxy-glycineamide (alpha-HGA), that is responsible for the antiviral activity. We show that alpha-HGA inhibits the replication of clinical HIV-1 isolates with acquired resistance to reverse transcriptase and protease inhibitors but has no effect on the replication of any of 10 different RNA and DNA viruses. alpha-HGA affected the ability of the HIV-1 capsid protein to assemble into tubular or core structures in vitro and in vivo, probably by binding to the hinge region between the N- and C-terminal domains of the HIV-1 capsid protein as indicated by matrix-assisted laser desorption ionization-mass spectrometry results. As an antiviral compound, alpha-HGA has an unusually simple structure, a pronounced antiviral specificity, and a novel mechanism of antiviral action. As such, it might prove to be a lead compound for a new class of anti-HIV substances.
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4.
  • Saulo, Eleonor C., et al. (författare)
  • Willingness and ability to pay for artemisinin-based combination therapy in rural Tanzania
  • 2008
  • Ingår i: Malaria Journal. - London : BioMed Central. - 1475-2875. ; 7, s. 227-
  • Tidskriftsartikel (refereegranskat)abstract
    • The aim of this study was to analyse willingness to pay (WTP) and ability to pay (ATP) for ACT for children below five years of age in a rural setting in Tanzania before the introduction of artemisinin-based combination therapy (ACT) as first-line treatment for uncomplicated malaria. Socio-economic factors associated with WTP and expectations on anti-malaria drugs, including ACT, were also explored.MethodsStructured interviews and focus group discussions were held with mothers, household heads, health-care workers and village leaders in Ishozi, Gera and Ishunju wards in north-west Tanzania in 2004. Contingent valuation method (CVM) was used with "take-it-or-leave-it" as the eliciting method, expressed as WTP for a full course of ACT for a child and households' opportunity cost of ACT was used to assess ATP. The study included descriptive analyses with multivariate adjustment for potential confounding factors.ResultsAmong 265 mothers and household heads, 244 (92%, CI = 88%–95%) were willing to pay Tanzanian Shillings (TSh) 500 (US$ 0.46) for a child's dose of ACT, but only 55% (49%–61%) were willing to pay more than TSh 500. Mothers were more often willing to pay than male household heads (adjusted odds ratio = 2.1, CI = 1.2–3.6). Socio-economic status had no significant effect on WTP. The median annual non-subsidized ACT cost for clinical malaria episodes in an average household was calculated as US$ 6.0, which would represent 0.9% of the average total consumption expenditures as estimated from official data in 2001. The cost of non-subsidized ACT represented 7.0% of reported total annual expenditure on food and 33.0% of total annual expenditure on health care."Rapid effect," "no adverse effect" and "inexpensive" were the most desired features of an anti-malarial drug.ConclusionWTP for ACT in this study was less than its real cost and a subsidy is, therefore, needed to enable its equitable affordability. The decision taken in Tanzania to subsidize Coartem® fully at governmental health care facilities and at a consumer price of TSh 300–500 (US$ 0.28–0.46) at special designated shops through the programme of Accredited Drug Dispensing Outlets (ADDOs) appears to be well founded.
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5.
  • Lindh, Martin, 1981-, et al. (författare)
  • Predicting the Rate of Skin Penetration Using an Aggregated Conformal Prediction Framework
  • 2017
  • Ingår i: Molecular Pharmaceutics. - Washington : American Chemical Society (ACS). - 1543-8384 .- 1543-8392. ; 14:5, s. 1571-1576
  • Tidskriftsartikel (refereegranskat)abstract
    • Skin serves as a drug administration route, and skin permeability of chemicals is of significant interest in the pharmaceutical and cosmetic industries. An aggregated conformal prediction (ACP) framework was used to build models, for predicting the permeation rate (log K-p) of chemical compounds through human skin. The conformal prediction method gives as an output the prediction range at a given level of confidence for each compound, which enables the user to make a more informed decision when, for example, suggesting the next compound to prepare, Predictive models were built using;both the random forest and the support vector machine methods and were based on experimentally derived permeability data on 211 diverse compounds. The derived models were of similar predictive quality as compared to earlier published models but have the extra advantage of not only presenting a single predicted value for each, compound but also a reliable, individually assigned prediction range. The models use calculated descriptors and can quickly predict the skin permeation rate of new compounds.
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6.
  • Wettermark, Bjoern, et al. (författare)
  • Secondary prevention in a large stroke population - A study of patients' purchase of recommended drugs
  • 2008
  • Ingår i: Stroke. - New York : American Heart Association. - 0039-2499 .- 1524-4628. ; 39:10, s. 2880-2885
  • Tidskriftsartikel (refereegranskat)abstract
    • Background and Purpose - In this study, linked, anonymous data from The National Hospital Discharge Register and the Swedish Prescribed Drug Register were used for studying to what extent recommended drugs for secondary prevention after stroke and TIA were purchased by patients in the region of Stockholm, Sweden (2 million inhabitants). Methods - Data on purchased drugs for secondary stroke prevention during July 2005 to June 2006 by 17 902 patients > 18 years discharged after stroke or TIA during the period 1997 to June 2005 were analyzed by age, gender, and year of discharge. Results - Antiplatelets and warfarin were purchased by 87% of all stroke and 83% of all TIA patients, antihypertensives by 74% and 70%, and lipid lowering drugs by 41% and 39%, respectively. Conclusion - Time after discharge had only a minor influence on the proportion of patients purchasing the medicines.
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7.
  • Karypidis, A.-H., et al. (författare)
  • Deletion polymorphism of the UGT2B17 gene is associated with increased risk for prostate cancer and correlated to gene expression in the prostate
  • 2008
  • Ingår i: The Pharmacogenomics Journal. - Avenet, NJ : Nature Pub. Group. - 1470-269X .- 1473-1150. ; 8:2, s. 147-151
  • Tidskriftsartikel (refereegranskat)abstract
    • Metabolism of androgens includes glucuronidation, the major pathway of steroid elimination in several steroid target tissues. Glucuronidation is catalysed by UDP-glucuronosyltransferases (UGTs). UGT2B17 has been shown to be particularly active against androgens and is highly abundant in the prostate. Recently, we discovered that deletion of the UGT2B17 gene is associated with low or undetectable urinary testosterone levels. Here, we determined the phenotypic outcome of the deletion by quantifying the UGT2B17 mRNA expression in normal prostate tissues in individuals with different genotypes. Additionally, the frequency of UGT2B17 deletion polymorphism was studied in a Swedish population-based case–control study including 176 patients diagnosed with prostate cancer and 161 controls. We found that the individuals homozygous for the insertion allele expressed 30 times more UGT2B17 mRNA in prostate tissue than the heterozygotes. Carriers of the deletion allele had a significantly increased risk of prostate cancer (OR=2.07; 95% CI=1.32–3.25). In conclusion, these results show the UGT2B17 deletion polymorphism is associated with prostate cancer risk. 
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8.
  • Eklund, Martin, et al. (författare)
  • The application of conformal prediction to the drug discovery process
  • 2015
  • Ingår i: Annals of Mathematics and Artificial Intelligence. - : Springer Science+Business Media B.V.. - 1012-2443 .- 1573-7470. ; 74:1-2, s. 117-132
  • Tidskriftsartikel (refereegranskat)abstract
    • QSAR modeling is a method for predicting properties, e.g. the solubility or toxicity, of chemical compounds using machine learning techniques. QSAR is in widespread use within the pharmaceutical industry to prioritize compounds for experimental testing or to alert for potential toxicity during the drug discovery process. However, the confidence or reliability of predictions from a QSAR model are difficult to accurately assess. We frame the application of QSAR to preclinical drug development in an off-line inductive conformal prediction framework and apply it prospectively to historical data collected from four different assays within AstraZeneca over a time course of about five years. The results indicate weakened validity of the conformal predictor due to violations of the randomness assumption. The validity can be strengthen by adopting semi-off-line conformal prediction. The non-randomness of the data prevents exactly valid predictions but comparisons to the results of a traditional QSAR procedure applied to the same data indicate that conformal predictions are highly useful in the drug discovery process.
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9.
  • Eriksson, Irene, et al. (författare)
  • Persistence with dimethyl fumarate in relapsing-remitting multiple sclerosis : a population-based cohort study
  • 2018
  • Ingår i: European Journal of Clinical Pharmacology. - Berling : Springer Berlin/Heidelberg. - 0031-6970 .- 1432-1041. ; 74:2, s. 219-226
  • Tidskriftsartikel (refereegranskat)abstract
    • PURPOSE: To describe patients initiating dimethyl fumarate (DMF) and measure persistence with DMF, discontinuation, and switching in treatment-naïve DMF patients and patients switching to DMF from other multiple sclerosis disease-modifying treatments (DMTs).METHODS: A population-based cohort study of all Stockholm County residents initiating DMF from 9 May 2014 until 31 May 2017. All data were derived from a regional database that collects individual-level data on healthcare and drug utilization of all residents. The study outcomes were persistence with DMF and DMF discontinuation and switching to other DMTs. Persistence was measured as the number of days until either DMF discontinuation (treatment gap ≥ 60 days) or switching to another DMT.RESULTS: The study included 400 patients (median follow-up = 2.5 years). The majority had previously been treated with other DMTs (61%). Throughout the follow-up period, 124 patients (31%) discontinued DMF and 114 patients (29%) switched treatment. Overall, 34% of patients initiating DMF stopped treatment within 1 year and only 43% of patients remained on DMF at 2 years from treatment initiation.CONCLUSIONS: DMF had a rapid market uptake likely due to high expectations held by both patients and clinicians. However, persistence with DMF in routine clinical practice was found to be low.
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10.
  • Fredin, Maria Fritsch, 1970, et al. (författare)
  • The application and relevance of ex vivo culture systems for assessment of IBD treatment in murine models of colitis
  • 2008
  • Ingår i: Pharmacological Research. - : Elsevier BV. - 1043-6618 .- 1096-1186. ; 58:3-4, s. 222-231
  • Tidskriftsartikel (refereegranskat)abstract
    • The aim of this study was to investigate the relevance of mouse ex vivo cultures as a first screening model for new therapeutic agents of Inflammatory Bowel Disease (IBD). Two murine models (dextran sodium sulphate (DSS)-induced colitis and Gαi2-deficient mice) and two anti-inflammatory agents (methyl-prednisolone and the proteasome inhibitor MG132) were evaluated. The in vivo effects of methyl-prednisolone were assessed in both models. Ex vivo colonic tissue from both mouse models were cultured in the presence or absence of the drugs and TaqMan Low-Density arrays were used to assess the regulation of inflammatory genes before and after drug treatment. Colitis induced a similar inflammatory gene profile in both mouse models in in vivo studies and in ex vivo cultures. The differences encountered reflected the different phases of colitis in the models, e.g. innate cytokine/chemokine profile in the DSS model and T cell related markers in Gαi2-deficient mice. After steroid treatment, a similar pattern of genes was suppressed in the two mouse models. We confirmed the suppression of inflammatory gene expression for IL-1β, IL-6 and iNOS in ex vivo and in vivo colons from both mouse models by quantitative RT-PCR. Importantly, the inflammatory responses in the murine ex vivo culture system reflected the in vivo response in the inflamed colonic tissue as assessed by changes in inflammatory gene expression, suggesting that the murine culture system can be used for validation of future IBD therapies.
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