| 1. |
- Andreasson, Anna Nixon, et al.
(författare)
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Leptin and adiponectin : Distribution and associations with cardiovascular risk factors in men and women of the general population
- 2012
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Ingår i: American Journal of Human Biology. - : Wiley. - 1042-0533 .- 1520-6300. ; 24:5, s. 595-601
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: In view of the increasing prevalence of obesity worldwide, understanding the role of the recently discovered adipokines leptin and adiponectin is of high clinical relevance. The aim of the present study was to assess the association between levels of leptin and adiponectin with age, known cardiovascular risk factors and to establish whether there are differences between men and women of the general population.METHODS: A total of 98 men and 107 women of the general population, aged between 20 and 74 years, underwent a medical examination at a clinical research center and fasting morning blood samples were also taken.RESULTS: Leptin (mean 7.5 μg l(-1) in men and 16.0 μg l(-1) in women) and adiponectin (mean 7.3 mg l(-1) in men and 11.9 mg l(-1) in women) levels were higher in women than men (Ps < 0.001). Both leptin and adiponectin levels increased with advancing age in both men and women (Ps < 0.05). Leptin was highly associated with factors for metabolic syndrome in men while in women, leptin was highly associated with inflammatory factors. Adiponectin was associated with blood lipids in both men and women, and glucose homeostasis more in women than in men.CONCLUSIONS: Leptin and adiponectin levels were ∼2 times and 1.5 times higher in women than in men, respectively. In addition, although leptin and adiponectin were associated to CVD risk factors in both men and women, we observed differences in specific CVD risk factor groups between men and women. These differences may be due to different regulatory mechanisms and effects of these adipokines in men and women.
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| 2. |
- Dahlgren, Markus, et al.
(författare)
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Design, Synthesis, and Multivariate Quantitative Structure-Activity Relationship of Salicylanilides-Potent Inhibitors of Type III Secretion in Yersinia
- 2007
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Ingår i: Journal of Medicinal Chemistry. - : American Chemical Society (ACS). - 0022-2623 .- 1520-4804. ; 50:24, s. 6177-6188
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Tidskriftsartikel (refereegranskat)abstract
- Analogues to the salicylanilide N-(4-Chlorophenyl)-2-acetoxy-3,5-diiodobenzamide, 1a, an inhibitor of type III secretion (T3S) in Yersinia, were selected, synthesized, and biologically evaluated in three cycles. First, a set of analogues with variations in the salicylic acid ring moiety was synthesized to probe possible structural variation. A basic structure-activity relationship was established and then used to cherry-pick compounds from a principal component analysis score plot of salicylanilides to generate a second set. A third set with increased likelihood of biological activity was designed using D-optimal onion design. A quantitative structure-activity relationship model using hierarchical partial least-square regression to latent structures (Hi-PLS) was computed using PLS score vectors of building blocks correlated to the % inhibition of T3S as a response. A PLS discriminant analysis (PLS-DA) model was derived using the same descriptor set as that for the Hi-PLS model. Both models were validated with an external test set.
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| 3. |
- Kauppi, Anna M., 1971-, et al.
(författare)
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Inhibitors of type III secretion in Yersinia : design, synthesis and multivariate QSAR of 2-sulfonamino-benzanilides
- 2007
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Ingår i: Bioorganic & Medicinal Chemistry. - : Elsevier Ltd. - 0968-0896 .- 1464-3391. ; 15:22, s. 6994-7011
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Compound 1, 2-(benzo[1,2,5]thiadiazole-4-sulfonylamino)-5-chloro-N-(3,4-dichloro-phenyl)-benzamide, was identified as a putative type III secretion inhibitor in Yersinia, and the compound thus has a potential to be used to prevent or treat bacterial infections. A set of seven analogues was synthesized and evaluated in a type III secretion dependent reporter-gene assay with viable bacterial to give basic SAR. A second set of 19 compounds was obtained by statistical molecular design in the building block and product space and subsequent synthesis. Evaluation in the reporter-gene assay showed that the compounds ranged from non-active to compounds more potent than 1. Based on the data multivariate QSAR models were established and the final Hi-PLS model showed good correlation between experimentally determined % inhibition and the calculated % inhibition of the reporter-gene signal.
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| 4. |
- Undén, Anna-Lena, et al.
(författare)
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Gender Differences in Self-Rated Health, Quality of Life, Quality of Care, and Matebolic Control in Patients with Diabetes
- 2008
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Ingår i: Gender Medicine. - : Elsevier BV. - 1550-8579 .- 1878-7398. ; 5:2, s. 162-180
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Tidskriftsartikel (refereegranskat)abstract
- Background: Because the projected increase in the number of diabetic patients is expected to strain the capabilities of health care providers worldwide, we are challenged to find ways of reducing the burden of diabetes. Maintaining and improving health-related quality of life (QoL) for diabetic patients may be viewed as public health goals.Objective: The aim of this cross-sectional study was to compare different aspects of health, QoL, and quality of care (QoC) between men and women with diabetes as a basis for planning and managing diabees care.Methods: All patients in 2 age groups (aged 20–30 years [younger age group] and aged 50–60 years [middle-aged group]) who were registered with the Department of Endocrinology, Metabolism, and Diabetes at Karolinska University Hospital, Stockholm, Sweden, in October 2004, were recruited for a survey. Questions were included about self-rated health (SRH), QoL, QoC, diabetes-related worries, occupational status, physical activity level, living arrangements, and educational background. Glycosylated hemoglobin (HbA1c) values were obtained from medical records.Results: Of the 223 eligible patients (109 men, 114 women) in the younger age group, 49 men and 74 women responded to the questionnaire; of the 300 eligible patients (170 men, 130 women) in the middle-aged group, 120 men and 93 women responded. Middle-aged women rated their mental well-being and QoL as worse compared with men (P < 0.001 and P < 0.05, respectively). In both age groups, women reported more diabetes-related worries and less ability to cope (P < 0.05 for the younger age group and P < 0.001 for the middle-aged group for both variables), thus the differences were more marked for middleaged women. Although there were no gender differences in metabolic control, middle-aged women reported less satisfaction with diabetes care (P < 0.001). Higher HbA1c was related to worse SRH in both men and women when analyzing the age groups together (P < 0.05). This association was most prominent in young women, in whom having more diabetes-related worries was also related to higher HbA1c (P < 0.01).Conclusion: In this study, women with diabetes appeared to have worse QoL and mental well-being compared with men with diabetes. Therefore, identifying strategies to improve SRH and QoL among diabetic patients, especially among women, is of great importance.
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| 5. |
- Undén, Anna-Lena, et al.
(författare)
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Inflammatory cytokines, behaviour and age as determinants of self-rated health in women
- 2007
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Ingår i: Clinical Science. - 0143-5221 .- 1470-8736. ; 112:5-6, s. 363-373
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Tidskriftsartikel (refereegranskat)abstract
- Self-rated health is a powerful and independent predictor of long-term health, but its biological basis is unknown. We have shown previously that self-rated health is associated with increased levels of circulating cytokines in women. The main aim of the present study was to increase the understanding of the association between markers of wellbeing, such as self-rated health, and cytokines and to investigate the impact of age on these associations. In 174 female consecutive primary health care patients divided into three age groups, we examined subjective ratings of health and aspects of wellbeing and circulating levels of IL (interleukin)-1beta, IL-1ra (IL-1 receptor antagonist), IL-6 and TNF-alpha (tumour necrosis factor-alpha). Poor self-rated health was significantly associated with higher levels of TNF-alpha in all of the age groups. For IL-1beta and IL-1ra, the correlations with self-rated health were significant only in the oldest age group. Lower ratings of other measurements of health and wellbeing were related to higher levels of cytokines, most pronounced for TNF-alpha and IL-1beta, and in the middle and olderst age groups. More symptoms resembling a sickness response induced by inflammation were implicated to be associated with lower self-rated health. The strength of the association between inflammatory cytokines and poor health perception increased with advanced age, indicating an increased vulnerability for inflammatory activity during aging. It is suggested that higher levels of TNF-alpha are connected to a sickness response that, in turn, is connected to self-rated health. The results provide a possible psychobiological basis to understand better diffuse subjective symptoms and poor subjective health in women.
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| 6. |
- Andersson, C David, et al.
(författare)
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Discovery of Ligands for ADP-Ribosyltransferases via Docking-Based Virtual Screening
- 2012
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Ingår i: Journal of Medicinal Chemistry. - : American Chemical Society (ACS). - 0022-2623 .- 1520-4804. ; 55:17, s. 7706-7718
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Tidskriftsartikel (refereegranskat)abstract
- The diphtheria toxin-like ADP-ribosyltransferases (ARTDs) are an enzyme family that catalyses the transfer of ADP-ribose units onto substrate proteins, using nicotinamide adenine dinucleotide (NAD(+)) as a co-substrate. They have a documented role in chromatin remodelling and DNA repair; and inhibitors of ARTD1 and 2 (PARP1 and 2) are currently in clinical trials for the treatment of cancer. The detailed function of most other ARTDs is still unknown. Using virtual screening we identified small ligands of ARTD7 (PARP15/BAL3) and ARTD8 (PARP14/BAL2). Thermal-shift assays confirmed that 16 compounds, belonging to eight structural classes, bound to ARTD7/ARTD8. Affinity measurements with isothermal titration calorimetry for two isomers of the most promising hit compound confirmed binding in the low micromolar range to ARTD8. Crystal structures showed anchoring of the hits in the nicotinamide pocket. These results form a starting point in the development of chemical tools for the study of the role and function of ARTD7 and ARTD8.
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| 7. |
- Andersson, Sara-Linnea, et al.
(författare)
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Plug-in Hybrid Electric Vehicles as Regulating Power Providers - Case Studies of Sweden and Germany
- 2010
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Ingår i: Energy Policy. - : Elsevier BV. - 0301-4215. ; 38:6, s. 2751-2762
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Tidskriftsartikel (refereegranskat)abstract
- This study investigates plug-in hybrid electric vehicles (PHEVs) as providers of regulating power in the form of primary, secondary and tertiary frequency control. Previous studies have shown that PHEVs could generate substantial profits while providing ancillary services. This study investigates under what conditions PHEVs can generate revenues using actual market data, i.e. prices and activations of regulating power, from Sweden and Germany from four months in 2008. PHEV market participation is modelled for individual vehicles in a fleet subject to a simulated movement pattern. Costs for infrastructure and vehicle-to-grid equipment are not included in the analysis. The simulation results indicate that maximum average profits generated on the German markets are in the range 30–80 h per vehicle and month whereas the Swedish regulating power markets give no profit.In addition, an analysis is performed to identify strengths, weaknesses, opportunities, and threats (SWOT) of PHEVs as regulating power providers. Based on the simulation results and the SWOT analysis, characteristics for an ideal regulating power market for PHEVs are presented.
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| 8. |
- Basmarke-Wehelie, Rahma, et al.
(författare)
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The complement regulator CD46 is bactericidal to Helicobacter pylori and blocks urease activity
- 2011
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Ingår i: Gastroenterology. - Baltimore : Elsevier BV. - 0016-5085 .- 1528-0012. ; 141:3, s. 918-928
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND & AIMS: CD46 is a C3b/C4b binding complement regulator and a receptor for several human pathogens. We examined the interaction between CD46 and Helicobacter pylori (a bacterium that colonizes the human gastric mucosa and causes gastritis), peptic ulcers, and cancer.METHODS: Using gastric epithelial cells, we analyzed a set of H pylori strains and mutants for their ability to interact with CD46 and/or influence CD46 expression. Bacterial interaction with full-length CD46 and small CD46 peptides was evaluated by flow cytometry, fluorescence microscopy, enzyme-linked immunosorbent assay, and bacterial survival analyses.RESULTS: H pylori infection caused shedding of CD46 into the extracellular environment. A soluble form of CD46 bound to H pylori and inhibited growth, in a dose- and time-dependent manner, by interacting with urease and alkyl hydroperoxide reductase, which are essential bacterial pathogenicity-associated factors. Binding of CD46 or CD46-derived synthetic peptides blocked the urease activity and ability of bacteria to survive in acidic environments. Oral administration of one CD46 peptide eradicated H pylori from infected mice.CONCLUSIONS: CD46 is an antimicrobial agent that can eradicate H pylori. CD46 peptides might be developed to treat H pylori infection.
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| 9. |
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| 10. |
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| 11. |
- Björklund, Camilla, 1977, et al.
(författare)
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Preschool class students’ discernment of number structure in a spatial pattern.
- 2024
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Ingår i: In Häggström, J., Kilhamn, C., Mattsson, L., Palmér, H., Perez, M., Pettersson. K., Röj-Lindberg, A.-S. & Teledahl, A. (Eds.), Mediating mathematics. Proceedings of MADIF14 (pp. 85–96).. - : SMDF.
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Konferensbidrag (refereegranskat)
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| 12. |
- Cappelletto, Elia, et al.
(författare)
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Impact of Post Manufacturing Handling of Protein-Based Biologic Drugs on Product Quality and User Centricity
- 2024
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Ingår i: Journal of Pharmaceutical Sciences. - : Elsevier B.V.. - 0022-3549 .- 1520-6017.
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Forskningsöversikt (refereegranskat)abstract
- This article evaluates the current gaps around the impact of post-manufacturing processes on the product qualities of protein-based biologics, with a focus on user centricity. It includes the evaluation of the regulatory guidance available, describes a collection of scientific literature and case studies to showcase the impact of post-manufacturing stresses on product and dosing solution quality. It also outlines the complexity of clinical handling and the need for communication, and alignment between drug providers, healthcare professionals, users, and patients. Regulatory agencies provide clear expectations for drug manufacturing processes, however, guidance supporting post-product manufacturing handling is less defined and often misaligned. This is problematic as the pharmaceutical products experience numerous stresses and processes which can potentially impact drug quality, safety and efficacy. This article aims to stimulate discussion amongst pharmaceutical developers, health care providers, device manufacturers, and public researchers to improve these processes. Patients and caregivers' awareness can be achieved by providing relevant educational material on pharmaceutical product handling.
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| 13. |
- Cappelletto, Elia, et al.
(författare)
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Impact of Post Manufacturing Handling of Protein-Based Biologic Drugs on Product Quality and User Centricity
- 2024
-
Ingår i: Journal of Pharmaceutical Sciences. - : Elsevier. - 0022-3549 .- 1520-6017.
-
Tidskriftsartikel (refereegranskat)abstract
- This article evaluates the current gaps around the impact of post-manufacturing processes on the product qualities of protein-based biologics, with a focus on user centricity. It includes the evaluation of the regulatory guidance available, describes a collection of scientific literature and case studies to showcase the impact of post-manufacturing stresses on product and dosing solution quality. It also outlines the complexity of clinical handling and the need for communication, and alignment between drug providers, healthcare professionals, users, and patients. Regulatory agencies provide clear expectations for drug manufacturing processes, however, guidance supporting post-product manufacturing handling is less defined and often misaligned. This is problematic as the pharmaceutical products experience numerous stresses and processes which can potentially impact drug quality, safety and efficacy. This article aims to stimulate discussion amongst pharmaceutical developers, health care providers, device manufacturers, and public researchers to improve these processes. Patients and caregivers' awareness can be achieved by providing relevant educational material on pharmaceutical product handling.
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| 14. |
- Dahlgren, Markus K, et al.
(författare)
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Statistical molecular design of a focused salicylidene acylhydrazide library and multivariate QSAR of inhibition of type III secretion in the Gram-negative bacterium Yersinia
- 2010
-
Ingår i: Bioorganic & Medicinal Chemistry. - : Elsevier BV. - 0968-0896 .- 1464-3391. ; 18:7, s. 2686-2703
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Tidskriftsartikel (refereegranskat)abstract
- A combined application of statistical molecular design (SMD), quantitative structure-activity relationship (QSAR) modeling and prediction of new active compounds was effectively used to develop salicylidene acylhydrazides as inhibitors of type III secretion (T3S) in the Gram-negative pathogen Yersinia pseudotuberculosis. SMD and subsequent synthesis furnished 50 salicylidene acylhydrazides in high purity. Based on data from biological evaluation in T3S linked assays 18 compounds were classified as active and 25 compounds showed a dose-dependent inhibition. The 25 compounds were used to compute two multivariate QSAR models and two multivariate discriminant analysis models were computed from both active and inactive compounds. Three of the models were used to predict 4416 virtual compounds in consensus and eight new compounds were selected as an external test set. Synthesis and biological evaluation of the test set in Y. pseudotuberculosis and the intracellular pathogen Chlamydia trachomatis validated the models. Y. pseudotuberculosis and C. trachomatis cell-based infection models showed that compounds identified in this study are selective and non-toxic inhibitors of T3S dependent virulence.
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| 15. |
- Ekblad, Torun, et al.
(författare)
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Towards small molecule inhibitors of mono-ADP-ribosyltransferases
- 2015
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Ingår i: European Journal of Medicinal Chemistry. - : Elsevier BV. - 0223-5234 .- 1768-3254. ; 95, s. 546-551
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Tidskriftsartikel (refereegranskat)abstract
- Protein ADP-ribosylation is a post-translational modification involved in DNA repair, protein degradation, transcription regulation, and epigenetic events. Intracellular ADP-ribosylation is catalyzed predominantly by ADP-ribosyltransferases with diphtheria toxin homology (ARTDs). The most prominent member of the ARTD family, poly(ADP-ribose) polymerase-1 (ARTD1/PARP1) has been a target for cancer drug development for decades. Current PARP inhibitors are generally non-selective, and inhibit the mono-ADP-ribosyltransferases with low potency. Here we describe the synthesis of acylated amino benzamides and screening against the mono-ADP-ribosyltransferases ARTD7/PARP15, ARTD8/PARP14, ARTD10/PARP10, and the poly-ADP-ribosyltransferase ARTD1/PARP1. The most potent compound inhibits ARTD10 with sub-micromolar IC50.
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| 16. |
- Elofsson, Anna Katarina, 1983
(författare)
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Climate Policy for Aviation - Analyses of measures at multiple levels
- 2019
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The aviation sector is affected by local, national, multinational (EU) and/or global climate policies targeting domestic, intra-European and intercontinental flights in different and partly overlapping ways. The aim of this thesis is to strengthen further knowledge on climate policy for aviation at multiple governance levels and by doing so contribute to a more informed policy process. This work is done by analysing climate policy, by both qualitative document analysis and energy-economic modelling, concerning aviation. Our results show that actions to reduce aviation emissions are taken at all geographical levels of governance. On the local level, a surprisingly large share, more than a quarter, of the cities studied are taking policy initiatives to reduce aviation. Moreover, we have recognized that cities tend to choose the system boundary (consumption or territorial perspective) that results in the lowest reported emissions. The major perceived conflict of interest at the local level is economic growth vs reduced air travel. With limited authority within the local setting, such as in the case of aviation emissions, governing by ‘agenda setting’ can be an important channel for cities to express their concerns and support change at higher levels. On the national level, some countries have policies such as passenger taxes, biofuel blending mandates (from 2020 in Norway) and carbon taxes on jet fuel. National policies in a country within the European Economic Area (EEA) will overlap fully with CORSIA and/or the EU ETS, which adds challenges regarding additionality of the emissions said to be reduced due by the different policies. Further, there is a potential for national policies to be spread and thereby achieve cumulative emissions reduction.
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| 17. |
- Elofsson, Anna Katarina, 1983, et al.
(författare)
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Local Governance of Greenhouse Gas Emissions from Air Travel
- 2018
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Ingår i: Journal of Environmental Policy and Planning. - 1523-908X .- 1522-7200. ; 20:5, s. 578-594
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Tidskriftsartikel (refereegranskat)abstract
- Global greenhouse gas emissions from air travel (GHG-A) are on the rise, and projections point towards a rapid growth in the coming decades. This study aims to examine how local government (cities), addresses GHG-A in their Sustainable Energy Action Plans (SEAP). To fulfil this aim, over 200 SEAPs were analysed focusing on three issues: (1) Treatment of GHG-A in local emissions inventories; (2) Policy initiatives within this domain; and (3) The cities’ perceptions of the conflicts of interests. Results showed that more than half of the cities acknowledge the challenge of GHG-A, around one third include GHG-A in their emissions inventories, and more than one quarter have initiated policy interventions. To categorise these interventions, we have added a mode ‘governing by agenda setting’ to an existing analytical framework, ‘Modes of governing’. With their authority limited to the local setting, this mode of governing is a common channel for cities to push changes at higher levels.
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| 18. |
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| 19. |
- Elofsson, Jessica, et al.
(författare)
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Supporting or restricting mathematical communication and reasoning in teaching 6-year olds
- 2023
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Ingår i: EARLI 2023. ; , s. 446-446
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Konferensbidrag (refereegranskat)abstract
- Communication and reasoning in mathematics is described as important for student learning. Hence, teachers have a central role to invite students to engage in reasoning and collective problem solving. One common way to promote this is for the teacher to ask questions. However, there is limited knowledge of how teachers make use of the input provided by students on the asked questions in their mathematics teaching to support further learning and mathematical inquiry. In the present study, we investigated qualitative differences in how preschool class teachers responded to and incorporated 6-year old students’ input in teaching about numbers and arithmetic. The data gathered for analysis consisted of fieldnotes collected through observations of 145 mathematics teaching episodes in 95 classes. To make it possible to map the qualitative different ways teachers responded to and incorporated students’ input in their teaching, the Mediating Primary Mathematics framework was used as an analytical tool. The results show that teachers responded to and incorporated student input in different ways in their teaching. In almost 2/3 of the teaching episodes, teachers stopped at only briefly confirming the input given as right or wrong, or just gave generally encouraging responses to the student. In just under 1/3 of the teaching episodes, teachers took advantage of and incorporated student input in their teaching to advance and verify their mathematical reasoning. This highlights that teachers may develop their ways of responding to and elaborating on students’ input in teaching, which could improve students’ opportunities for learning mathematics.
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| 20. |
- Elofsson, Jessica, et al.
(författare)
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Teachers incorporating 6-yearolds’ input in mathematics teaching
- 2022
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Ingår i: Oral Communication, in C. Fernández, S. Llinares, A. Gutiérrez, & N. Planas (Eds.), Proceedings of the 45th Conference of the International Group for the Psychology of Mathematics Education (Vol. 4, p. 203). - Alicante : PME. - 9788413021782
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Konferensbidrag (refereegranskat)
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| 21. |
- Elofsson, Jessica, et al.
(författare)
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Teachers incorporating 6-yearolds’ input in mathematics teaching
- 2022
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Ingår i: Proceedings of the 45th Conference of the International Group for the Psychology of Mathematics Education. - : Psychology in Mathematics Education (PME). - 9788413021782 ; , s. 203-
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Konferensbidrag (refereegranskat)abstract
- The potential for student mathematics learning lies both in the teacher ability to ask questions and to follow up and incorporate student input into the teaching of a specific content (Murata, 2015). Swedish students are expected to engage in reasoning and collective problem solving in highly communicative teaching practice. To improve these learning situations, it is important to understand how teachers are making use of student input in teaching. In this study we seek to map and understand how teachers in preschool classes respond to and incorporate student input in mathematics teaching.This paper reports on findings from a study focusing on mathematics teaching in preschool classes in Sweden (6-yearolds). The data consist of 145 observations (from 95 individual teachers) of mathematics teaching relating to whole numbers. The data for analysis consist of fieldnotes and was collected during fall 2021. The MPM-framework “Mediating Primary Mathematics” (Venkat & Askew, 2018) was used as an analytical tool to identify the ways teachers in preschool classes respond to and incorporate student input in their mathematics teaching. Following the four levels in the framework, the results show that in 61,4% of the observations, teachers give students very little opportunity to contribute with input beyond short responses, merely confirming or giving generally encouraging responses to the student. This is to becompared to 29,7% of the observations, where teachers take advantage of student input by incorporating these into the teaching situation to advance or verify students’ mathematical reasoning. In the third largest group (8.3 % of the observations), the teachers pulled back or made no evaluation of the student input. Only in one case (0.7% of the observations), the teacher took advantage of the student input and both advanced and explained it further to support learner progression.The results raise questions about how teachers’ ways of responding to and elaborating on students’ input might influence students’ opportunities for learning about numbers. In particular, when teachers advance, verify, and explain student input, significant connections and justifications for solution methods are highlighted.
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| 22. |
- Elofsson, Ulla, et al.
(författare)
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Pulmonary delivery of antimicrobial peptides
- 2015
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Ingår i: ONdrugDelivery. - 2049-145X .- 2049-1468. ; 57, s. 4-7
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Tidskriftsartikel (refereegranskat)abstract
- Anna Fureby, PhD, Group Manager & Senior Scientist, Life Science, and Ulla Elofsson, PhD, Senior Scientist, both of SP Technical Research Institute of Sweden, and Per Gerde, PhD, Chief Scientific Officer, Inhalation Sciences Sweden, discuss the serious problem of antibiotic resistance and the potential role of antimicrobial peptides in the treatment of resistant bacterial strains. For pulmonary infections, optimising the formulation and delivery method is a crucial factor for success.
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| 23. |
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| 24. |
- Elversson, J, et al.
(författare)
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Droplet and particle size relationship and shell thickness of inhalable lactose particles during spray drying
- 2003
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Ingår i: Journal of Pharmaceutical Sciences. - : Wiley. - 0022-3549 .- 1520-6017. ; 92, s. 900-910
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Tidskriftsartikel (refereegranskat)abstract
- To find means of controlling the size and density of particles intended for inhalation the relationship between droplet and particle size during spray drying was investigated. Lactose solutions were atomized with a two-fluid nozzle and dried in a laboratory spray drier. The effects of nozzle orifice diameter, atomization airflow and feed concentration on droplet and particle size were examined. Mass median diameter of both droplets and particles were analyzed with laser diffraction. In addition, scanning electron microscopy and transmission electron microscopy were used for studies of particle shape and morphology. It was demonstrated that nozzle orifice diameter and airflow, but not feed concentration controlled the droplet size during atomization. Increasing droplet size increased particle size but the effect was also influenced by feed concentration. Particles from solutions of a low concentration (1% w/w) were smaller than those from higher concentrations (5-20% w/w). This may be partly explained by lower yields at higher feed concentrations, but may also be related to differences in drying rate. Spray-dried lactose solutions formed hollow particles, and it was suggested that the shell thickness of the particles increased with increasing feed concentration
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| 25. |
- Gwon, Yong-Dae, et al.
(författare)
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Antiviral Activity of Benzavir-2 against Emerging Flaviviruses
- 2020
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Ingår i: Viruses. - : MDPI. - 1999-4915. ; 12:3
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Tidskriftsartikel (refereegranskat)abstract
- Most flaviviruses are arthropod-borne viruses, transmitted by either ticks or mosquitoes, and cause morbidity and mortality worldwide. They are endemic in many countries and have recently emerged in new regions, such as the Zika virus (ZIKV) in South-and Central America, the West Nile virus (WNV) in North America, and the Yellow fever virus (YFV) in Brazil and many African countries, highlighting the need for preparedness. Currently, there are no antiviral drugs available to treat flavivirus infections. We have previously discovered a broad-spectrum antiviral compound, benzavir-2, with potent antiviral activity against both DNA- and RNA-viruses. Our purpose was to investigate the inhibitory activity of benzavir-2 against flaviviruses. We used a ZIKV ZsGreen-expressing vector, two lineages of wild-type ZIKV, and other medically important flaviviruses. Benzavir-2 inhibited ZIKV derived reporter gene expression with an EC50 value of 0.8 +/- 0.1 µM. Furthermore, ZIKV plaque formation, progeny virus production, and viral RNA expression were strongly inhibited. In addition, 2.5 µM of benzavir-2 reduced infection in vitro in three to five orders of magnitude for five other flaviviruses: WNV, YFV, the tick-borne encephalitis virus, Japanese encephalitis virus, and dengue virus. In conclusion, benzavir-2 was a potent inhibitor of flavivirus infection, which supported the broad-spectrum antiviral activity of benzavir-2.
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| 26. |
- Halthur, Tobias, et al.
(författare)
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Self-assembly/aggregation behavior and adsorption of enamel matrix derivate protein to silica surfaces
- 2006
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Ingår i: Langmuir. - : American Chemical Society (ACS). - 0743-7463 .- 1520-5827. ; 22:5, s. 2227-2234
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Tidskriftsartikel (refereegranskat)abstract
- Adsorption of the amelogein protein mixture enamel matrix derivate (EMD) to silica surfaces has been studied by in situ ellipsometry and quartz crystal microbalance with dissipation (QCM-D). The protein was found to adsorb as nanospheres in mono- or multilayers, depending on the concentration of "free" nanospheres available in solution. The concentration of free nanospheres is determined by the competitive processes of adsorption and rapid aggregation into microscopic particles, measured by dynamic light scattering (DLS). Multilayers could also be formed by sequential injections of fresh EMD solution. At higher temperature, an up to 6 times thicker gel-like film was formed on the substrate surface, and decreasing the pH lead to disruption of the multi layer/aggregate formation and a decreased amount adsorbed.
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| 27. |
- Happonen, Maija, et al.
(författare)
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Aviation's climate impact allocated to inbound tourism: decision-making insights for "climate-ambitious" destinations
- 2023
-
Ingår i: Journal of Sustainable Tourism. - : Informa UK Limited. - 1747-7646 .- 0966-9582. ; 31:8, s. 1885-1901
-
Tidskriftsartikel (refereegranskat)abstract
- The climate impact from international aviation was 2.4% of the world's total climate impact in 2018, and is expected to grow. International regulation of this impact is not aligned with trajectories to stay below 1.5 degrees C of global warming. Conventional approaches to allocating climate impact to international aviation also lack one of the important drivers for air travel: tourism. Existing studies have focused on the carbon footprint of residents' outbound air travel, but there is a lack of focus on the climate impact from inbound air travel. This article quantifies the climate impact of inbound air travel, and presents it alongside the impact of outbound air travel, to get a full picture of the climate impact of tourism-driven air travel and provide insights for tourism's decision-makers. This was done in a case study for Sweden. The results show that the emissions from inbound air travel have grown 3 times more than emissions from outbound air travel each year, at a faster rate than the yearly growth for all international air travel. Responsibility for the climate impacts of inbound and outbound air travel is discussed, along with further actions such as demarketing and focusing on closer source markets.
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| 28. |
- Horvath, Dragos, et al.
(författare)
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Design of a general-purpose European compound screening library for EU-OPENSCREEN
- 2014
-
Ingår i: ChemMedChem. - : Wiley. - 1860-7179 .- 1860-7187. ; 9:10, s. 2309-2326
-
Tidskriftsartikel (refereegranskat)abstract
- This work describes a collaborative effort to define and apply a protocol for the rational selection of a general-purpose screening library, to be used by the screening platforms affiliated with the EU-OPENSCREEN initiative. It is designed as a standard source of compounds for primary screening against novel biological targets, at the request of research partners. Given the general nature of the potential applications of this compound collection, the focus of the selection strategy lies on ensuring chemical stability, absence of reactive compounds, screening-compliant physicochemical properties, loose compliance to drug-likeness criteria (as drug design is a major, but not exclusive application), and maximal diversity/coverage of chemical space, aimed at providing hits for a wide spectrum of drugable targets. Finally, practical availability/cost issues cannot be avoided. The main goal of this publication is to inform potential future users of this library about its conception, sources, and characteristics. The outline of the selection procedure, notably of the filtering rules designed by a large committee of European medicinal chemists and chemoinformaticians, may be of general methodological interest for the screening/medicinal chemistry community. The selection task of 200K molecules out of a pre-filtered set of 1.4M candidates was shared by five independent European research groups, each picking a subset of 40K compounds according to their own in-house methodology and expertise. An in-depth analysis of chemical space coverage of the library serves not only to characterize the collection, but also to compare the various chemoinformatics-driven selection procedures of maximal diversity sets. Compound selections contributed by various participating groups were mapped onto general-purpose self-organizing maps (SOMs) built on the basis of marketed drugs and bioactive reference molecules. In this way, the occupancy of chemical space by the EU-OPENSCREEN library could be directly compared with distributions of known bioactives of various classes. This mapping highlights the relevance of the selection and shows how the consensus reached by merging the five different 40K selections contributes to achieve this relevance. The approach also allows one to readily identify subsets of target-or target-class-oriented compounds from the EU-OPENSCREEN library to suit the needs of the diverse range of potential users. The final EU-OPENSCREEN library, assembled by merging five independent selections of 40K compounds from various expert groups, represents an excellent example of a Europe-wide collaborative effort toward the common objective of building best-in-class European open screening platforms.
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| 29. |
- Kauppi, Anna, 1971-
(författare)
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Chemical attenuation of bacterial virulence : small molecule inhibitors of type III secretion
- 2006
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Despite the large arsenal of antibiotics available on the market, treatment of bacterial infections becomes more challenging in view of the fact that microbes develop resistance against existing drugs. There is an obvious need for novel drugs acting on both old and new targets in bacteria. In this thesis we have employed a whole cell bacterial assay for screening and identification of type III secretion system (T3SS) inhibitors in Yersinia pseudotuberculosis. The T3SS is a common virulence mechanism utilized by several clinically relevant Gram-negative bacteria including Salmonella, Shigella, Pseudomonas aeruginosa, Chlamydiae and Escherichia coli. Several components in the T3SS have proved to be conserved and hence data generated with Y. pseudotuberculosis as model might also be valid for other bacterial species. We have screened a 9,400 commercial compound library for T3S inhibitors in Y. pseudotuberculosis using a yopE reporter gene assay. The initial ~ 30 hits were followed up in a growth inhibition assay resulting in 26 interesting compounds that were examined in more detail. Three of the most interesting compounds, salicylanilides, 2-hydroxybenzylidene-hydrazides and 2-arylsulfonamino-benzanilides, were selected for continued investigations. The inhibitor classes show different profiles regarding the effects on T3SS in Yersinia and their use as research tools and identification of the target proteins using a chemical biology approach will increase our understanding of bacterial virulence. The 2-hydroxybenzylidene-hydrazides have been extensively studied in vitro and show potential as selective T3S inhibitors in several Gram-negative pathogens besides Y. pseudotuberculosis. The data obtained suggest that this inhibitor class targets a conserved protein in the secretion apparatus. In cell-based ex vivo infection models T3SS was inhibited to the advantage of the infected eukaryotic cells. The salicylanilides and 2-arylsulfonamino-benzanilides have been further investigated by statistical molecular design (SMD) followed by synthesis and biological evaluation in the T3SS linked reporter gene assay. Multivariate QSAR models were established despite the challenges with data obtained from assays using viable bacteria. Our results indicate that this SMD QSAR strategy is powerful in development of virulence inhibitors targeting the T3SS.
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| 30. |
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| 31. |
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| 32. |
- Kauppi, Anna, 1971-, et al.
(författare)
-
Targeting bacterial Virulence : Inhibitors of type III secretion in Yersinia
- 2003
-
Ingår i: Chemistry and Biology. - 1074-5521 .- 1879-1301. ; 10:3, s. 241-249
-
Tidskriftsartikel (refereegranskat)abstract
- Agents that target bacterial virulence without detrimental effect on bacterial growth are useful chemical probes for studies of virulence and potential candidates for drug development. Several gram-negative pathogens employ type III secretion to evade the innate immune response of the host. Screening of a chemical library with a luciferase reporter gene assay in viable Yersinia pseudotuberculosis furnished several compounds that inhibit the reporter gene signal expressed from the yopE promoter and effector protein secretion at concentrations with no or modest effect on bacterial growth. The selectivity patterns observed for inhibition of various reporter gene strains indicate that the compounds target the type III secretion machinery at different levels. Identification of this set of inhibitors illustrates the approach of utilizing cell-based assays to identify compounds that affect complex bacterial virulence systems.
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| 33. |
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| 34. |
- Larsson, Jörgen, 1966, et al.
(författare)
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International and national climate policies for aviation: a review
- 2019
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Ingår i: Climate Policy. - : Informa UK Limited. - 1752-7457 .- 1469-3062. ; 19:6, s. 787-799
-
Forskningsöversikt (refereegranskat)abstract
- Aviation constitutes about 2.5% of all energy-related CO2 emissions and in addition there are non-CO2 effects. In 2016, the ICAO decided to implement a Carbon Offsetting and Reduction Scheme for International Aviation (CORSIA) and in 2017 the EU decided on faster emission reductions in its Emissions Trading System (EU ETS), which since 2012 includes the aviation sector. The effects of these policies on the expected development of air travel emissions from 2017 to 2030 have been analyzed. For the sample country Sweden, the analysis shows that when emissions reductions in other sectors are attributed to the aviation sector as a result of the EU ETS and CORSIA, carbon emissions are expected to reduce by -0.8% per year (however if non-CO2 emissions are included in the analysis, then emissions will increase). This is much less than what is needed to achieve the 2 degrees C target. Our analysis of potential national aviation policy instruments shows that there are legally feasible options that could mitigate emissions in addition to the EU ETS and CORSIA. Distance-based air passenger taxes are common among EU Member States and through increased ticket prices these taxes can reduce demand for air travel and thus reduce emissions. Tax on jet fuel is an option for domestic aviation and for international aviation if bilateral agreements are concluded. A quota obligation for biofuels is a third option.
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| 35. |
- Lindgren, Anders E. G., et al.
(författare)
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Chemical Probes to Study ADP-Ribosylation : Synthesis and Biochemical Evaluation of Inhibitors of the Human ADP-Ribosyltransferase ARTD3/PARP3
- 2013
-
Ingår i: Journal of Medicinal Chemistry. - : American Chemical Society (ACS). - 0022-2623 .- 1520-4804. ; 56:23, s. 9556-9568
-
Tidskriftsartikel (refereegranskat)abstract
- The racemic 3-(4-oxo-3,4-dihydroquinazolin-2-yl)-N-[1-(pyridin-2-yl)ethyl]propanamide, 1, has previously been identified as a potent but unselective inhibitor of diphtheria toxin-like ADP-ribosyltransferase 3 (ARTD3). Herein we describe synthesis and evaluation of SS compounds in this class. It was found that the stereochemistry is of great importance for both selectivity and potency and that substituents on the phenyl ring resulted in poor solubility. Certain variations at the meso position were tolerated and caused a large shift in the binding pose. Changes to the ethylene linker that connects the quinazolinone to the amide were also investigated but proved detrimental to binding. By combination of synthetic organic chemistry and structure-based design, two selective inhibitors of ARTD3 were discovered.
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| 36. |
- Lindgren, Anders E. G., et al.
(författare)
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PARP Inhibitor with Selectivity Toward ADP-Ribosyltransferase ARTD3/PARP3
- 2013
-
Ingår i: ACS Chemical Biology. - : American Chemical Society (ACS). - 1554-8929 .- 1554-8937. ; 8:8, s. 1698-1703
-
Tidskriftsartikel (refereegranskat)abstract
- Inhibiting ADP-ribosyl transferases with PARP-inhibitors is considered a promising strategy for the treatment of many cancers and ischemia, but most of the cellular targets are poorly characterized. Here, we describe an inhibitor of ADP-ribosyltransferase-3/poly(ADP-ribose) polymerase-3 (ARTD3), a regulator of DNA repair and mitotic progression. In vitro profiling against 12, members of the enzyme family suggests selectivity for ARTD3, and crystal structures illustrate the molecular basis for inhibitor selectivity. The compound is active in cells, where it elicits ARTD3-specific effects at submicromolar concentration. Our results show that by targeting the nicotinamide binding site, selective inhibition can be achieved among the closest relatives of the validated clinical target, ADP-ribosyltransferase-1/poly(ADP-ribose) polymerase-1.
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| 37. |
- Lindgren, Anders E G, et al.
(författare)
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Statistical molecular design : a tool to follow up hits from small-molecule screening.
- 2014
-
Ingår i: Methods in Molecular Biology. - Totowa, NJ : Springer. - 1064-3745 .- 1940-6029. ; 1056, s. 169-188
-
Tidskriftsartikel (refereegranskat)abstract
- In high-throughput screening (HTS) a robust assay is used to interrogate a large collection of small organic molecules in order to find compounds, hits, with a desired biological activity. The hits are then further explored by an iterative process where new compounds are designed, purchased, or synthesized, followed by an evaluation in one or more assays. Statistical molecular design (SMD) is a useful method to select a balanced, varied, and information-rich compound collection based on hits from HTS in order to create a foundation for development of optimized compounds with improved properties. In this chapter, we describe the use of SMD to explore a hit obtained from small-molecule screening.
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| 38. |
- Linusson, Anna, et al.
(författare)
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Statistical molecular design of balanced compound libraries for QSAR modeling
- 2010
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Ingår i: Current Medicinal Chemistry. - : Bentham Science Publishers Ltd.. - 0929-8673 .- 1875-533X. ; 17:19, s. 2001-2016
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Forskningsöversikt (refereegranskat)abstract
- A fundamental step in preclinical drug development is the computation of quantitative structure-activity relationship (QSAR) models, i.e. models that link chemical features of compounds with activities towards a target macromolecule associated with the initiation or progression of a disease. QSAR models are computed by combining information on the physicochemical and structural features of a library of congeneric compounds, typically assembled from two or more building blocks, and biological data from one or more in vitro assays. Since the models provide information on features affecting the compounds' biological activity they can be used as guides for further optimization. However, in order for a QSAR model to be relevant to the targeted disease, and drug development in general, the compound library used must contain molecules with balanced variation of the features spanning the chemical space believed to be important for interaction with the biological target. In addition, the assays used must be robust and deliver high quality data that are directly related to the function of the biological target and the associated disease state. In this review, we discuss and exemplify the concept of statistical molecular design (SMD) in the selection of building blocks and final synthetic targets (i.e. compounds to synthesize) to generate information-rich, balanced libraries for biological testing and computation of QSAR models.
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| 39. |
- Martínez, Clàudia Sabaté, et al.
(författare)
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Examination of the Protein Drug Supply Chain in a Swedish University Hospital : Focus on Handling Risks and Mitigation Measures
- 2023
-
Ingår i: Journal of Pharmaceutical Sciences. - : Elsevier. - 0022-3549 .- 1520-6017. ; 112:11, s. 2799-2810
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Tidskriftsartikel (refereegranskat)abstract
- Protein drugs, such as monoclonal antibodies, have proved successful in treating cancer and immune system diseases. The structural complexity of these molecules requires careful handling to ensure integrity and stability of the drug. In this study, a failure mode and effects analysis was performed based on a Gemba Walk method in a Swedish University Hospital. The Gemba Walk is focused on pharmacists observing the actual supply process steps from distributor, pharmacy cleanroom to patient administration. Relevant protein drugs are chosen based on sales statistics within the hospital and the corresponding wards were observed. Further is the Double Diamond design method used to identify major risks and deliver mitigation strategies. The study identified potential stress factors such as temperature, shock by impact, shaking, vibration and light exposure. There were also risks associated with porters’ and healthcare professionals’ lack of awareness and access to information. These risk factors may cause loss of efficacy and quality of the protein drug, potentially leading to patient safety concerns. In this study, a simulation is also performed to list measures that theoretically should be in place to ensure the quality of the protein drug, for example validated and protocol-based compounding in cleanroom, training and validated transports.
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| 40. |
- Millqvist-Fureby, Anna, et al.
(författare)
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Surface composition of spray-dried milk protein-stabilised emulsions in relation to pre-heat treatment of proteins
- 2001
-
Ingår i: Colloids and Surfaces B. - 0927-7765 .- 1873-4367. ; 21, s. 47-58
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Tidskriftsartikel (refereegranskat)abstract
- Several important technical properties of spray-dried food powders depend on particle-liquid interactions (e.g. wettability, dispersability) and particle-particle interactions (e.g. flowability). It can be assumed that the chemical composition of the surface layer of the particles to a large extent determine these properties. The present study has been aimed to investigate the relation between the surface composition of spray-dried milk protein-stabilised emulsions and pre-heat treatment of the proteins. Solutions of WPC were heat-treated at low (60-90°C) and high (140°C) temperature and the degree of denaturation was determined, prior to the preparation of emulsions with rapeseed oil. The surface composition of the dry powders were established by using ESCA (electron spectroscopy of chemical analysis).The emulsions were characterised by droplet size distribution before spray drying and after dissolution of the powders. Also free fat extractions and estimations of wettability (dissolution rates) were performed. The powder surface coverage of protein decreased with increasing degree of protein denaturation before the emulsification, whereas the emulsion droplet size increased both before spray drying and after reconstitution of powders. The free fat extraction as well as the dissolution rate, whereof the latter decreased with increasing surface fat coverage, correlated well with the fat coverage of the powder surface.
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| 41. |
- Mojica, Sergio, 1987-, et al.
(författare)
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Red Fluorescent Chlamydia trachomatis Applied to Live Cell Imaging and Screening for Antibacterial Agents
- 2018
-
Ingår i: Frontiers in Microbiology. - : Frontiers Media S.A.. - 1664-302X. ; 9
-
Tidskriftsartikel (refereegranskat)abstract
- In this study, we describe the application of a transformed Chlamydia trachomatis strain constitutively expressing the red fluorescent protein mCherry, to allow real-time monitoring of the infection cycle and screening for agents that block replication of C. trachomatis. The red fluorescent C. trachomatis strain was detected autonomously without antibody staining and was equally susceptible to doxycycline as the wild type strain. A high-throughput screening assay was developed using the transformed strain and automated fluorescence microscopy. The assay was used in a pilot screen of a 349 compound library containing natural products from Australian flora and fauna. Compounds with anti-chlamydial activity were tested for dose response and toxicity to host cells and two non-toxic compounds had 50% effective concentration (EC50) values in the low micromolar range. Natural products are valuable sources for drug discovery and the identified Chlamydia growth inhibition may be starting points for future drug development. Live cell imaging was used to visualize growth of the red fluorescent C. trachomatis strain over time. The screening assay reduced workload and reagents compared to an assay requiring immunostaining and could further be used to monitor the development of Chlamydia inclusions and anti-chlamydial effect in real time.
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| 42. |
- Nordfelth, R., et al.
(författare)
-
Small-molecule inhibitors specifically targeting type III secretion
- 2005
-
Ingår i: Infection and Immunity. - Washington : American Society for Microbiology. - 0019-9567 .- 1098-5522. ; 73:5, s. 3104-3114
-
Tidskriftsartikel (refereegranskat)abstract
- The type III secretion (TTS) system is used by several animal and plant pathogens to deliver effector proteins into the cytosol of the eukaryotic target cell as a strategy to evade the defense reactions elicited by the infected organism. The fact that these systems are highly homologous implies that novel antibacterial agents that chemically attenuate the pathogens via a specific interaction with the type III secretion mechanism can be identified. A number of small organic molecules having this potential have recently been identified (A. M. Kauppi, R. Nordfelth, H. Uvell, H. Wolf-Watz, and M. Elofsson, Chem. Biol. 10:241-249, 2003). Using different reporter gene constructs, we showed that compounds that belong to a class of acylated hydrazones of different salicylaldehydes target the TTS system of Yersinia pseudotuberculosis. One of these compounds, compound 1, was studied in detail and was found to specifically block Yop effector secretion under in vitro conditions by targeting the TTS system. In this respect the drug mimics the well-known effect of calcium on Yop secretion. In addition, compound I inhibits Yop effector translocation after infection of HeLa cells without affecting the eukaryotic cells or the bacteria. A HeLa cell model that mimics in vivo conditions showed that compound 1 chemically attenuates the pathogen to the advantage of the eukaryotic cell. Thus, our results show proof of concept, i.e., that small compounds targeting the TTS system can be identified, and they point to the possible use of TTS inhibitors as a novel class of antibacterial agents.
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| 43. |
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| 44. |
- Pudelko, Maciej, et al.
(författare)
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Formation of lactones from sialylated MUC1 glycopeptides
- 2006
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Ingår i: Organic and biomolecular chemistry. - : Royal Society of Chemistry (RSC). - 1477-0520 .- 1477-0539. ; 4:4, s. 713-20
-
Tidskriftsartikel (refereegranskat)abstract
- The tumor-associated carbohydrate antigens TN, T, sialyl TN and sialyl T are expressed on mucins in several epithelial cancers. This has stimulated studies directed towards development of glycopeptide-based anticancer vaccines. Formation of intramolecular lactones involving sialic acid residues and suitably positioned hydroxyl groups in neighboring saccharide moieties is known to occur for glycolipids such as gangliosides. It has been suggested that these lactones are more immunogenic and tumor-specific than their native counterparts and that they might find use as cancer vaccines. We have now investigated if lactonization also occurs for the sialyl TN and T antigens of mucins. It was found that the model compound sialyl T benzyl glycoside , and the glycopeptide Ala-Pro-Asp-Thr-Arg-Pro-Ala from the tandem repeat of the mucin MUC1, in which Thr stands for the 2,3-sialyl-T antigen, lactonized during treatment with glacial acetic acid. Compound gave the 1''--> 2' lactone as the major product and the corresponding 1''--> 4' lactone as the minor product. For glycopeptide the 1''--> 4' lactone constitued the major product, whereas the 1''--> 2' lactone was the minor one. When lactonized was dissolved in water the 1''--> 4' lactone underwent slow hydrolysis, whereas the 1''--> 2' remained stable even after a 30 days incubation. In contrast the corresponding 2,6-sialyl-TN glycopeptide did not lactonize in glacial acetic acid.
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| 45. |
- Sabaté-Martínez, Clàudia, et al.
(författare)
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How are we handling protein drugs in hospitals? A human factors and systems engineering approach to compare two hospitals and suggest a best practice
- 2024
-
Ingår i: International Journal for Quality in Health Care. - : Oxford University Press. - 1353-4505 .- 1464-3677. ; 36:1
-
Tidskriftsartikel (refereegranskat)abstract
- Biopharmaceuticals are complex biological molecules that require careful storage and handling to ensure medication integrity. In this study, a work system analysis of real-world protein drug (PD) handling was performed with the following goals: identify main barriers and facilitators for successful adherence to accepted recommendations in PD handling, analyse differences in two organizations, and define a Best Current Practice in the real-life handling of PDs based on the results of the work system analysis. Observational study was held in two university hospitals in Spain and Sweden. Based on the Systems Engineering Initiative for Patient Safety (SEIPS) model, the tools chosen were: the PETT scan, in order to indicate the presence of barriers or facilitators for the PETT components (People, Environment, Tools, Tasks); the Tasks and tools matrices to construct a checklist to record direct observations during the real-life handling of biopharmaceuticals, and the Journey map to depict the work process. Observations were performed between March and November 2022. Each episode of direct observation included a single protein drug in some point of the supply chain and considered all the elements in the work system. Based on the results of the work system analysis and the literature review, the authors propose a list of items which could be assumed as Best Current Practice for PDs handling in hospitals. There were a total of 34 observations involving 19 PDs. Regarding People involved in the work process, there was a diversity of professionals with different previous training and knowledge, leading to an information gap. With respect to Environment, some structural and organizational differences between hospitals lead to risks related to the time exposure of PDs to room temperature and mechanical stress. Some differences also existed in the Tools and Tasks involved in the process, being especially relevant to the lack of compatibility information of PDs with new technologies, such as pneumatic tube system, robotic reconstitution, or closed-system transfer devices. Finally, 15 suggestions for best current practice are proposed. Main barriers found for compliance with accepted recommendations were related to the information gap detected in professionals involved in the handling of protein drugs, unmonitored temperature, and the lack of compatibility information of protein drugs with some new technologies. By applying a Human Factors and Systems Engineering Approach, the comparison of two European hospitals has led to a suggested list of Best Current Practices in the handling of protein drugs in a hospital.
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| 46. |
- Saleeb, Michael, et al.
(författare)
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Natural product inspired library synthesis – Identification of 2,3-diarylbenzofuran and 2,3-dihydrobenzofuran based inhibitors of Chlamydia trachomatis
- 2018
-
Ingår i: European Journal of Medicinal Chemistry. - : Elsevier. - 0223-5234 .- 1768-3254. ; 143, s. 1077-1089
-
Tidskriftsartikel (refereegranskat)abstract
- A natural product inspired library was synthesized based on 2,3-diarylbenzofuran and 2,3-diaryl-2,3-dihydrobenzofuran scaffolds. The library of forty-eight compounds was prepared by utilizing Pd-catalyzed one-pot multicomponent reactions and ruthenium-catalyzed intramolecular carbenoid C-H insertions. The compounds were evaluated for antibacterial activity in a panel of test systems including phenotypic, biochemical and image-based screening assays. We identified several potent inhibitors that block intracellular replication of pathogenic Chlamydia trachomatis with IC50 ≤ 3 μM. These new C. trachomatis inhibitors can serve as starting points for the development of specific treatments that reduces the global burden of C. trachomatis infections.
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| 47. |
- Saleeb, Michael, 1985-
(författare)
-
Towards novel antibacterials : Synthesis and identification of natural product inspired inhibitors of Chlamydia trachomatis and development of chemical probes targeting virulence of Pseudomonas aeruginosa
- 2018
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Antibiotic resistance has evolved significantly to become one of the serious threats to public health today. Yet, the pipeline of new antibiotics is drying up and is lagging behind the challenging needs. As a contribution to this recurrent need for novel antibacterials, we applied multidisciplinary strategies to identify small-molecule antibacterials against Chlamydia trachomatis and antivirulence agents against Pseudomonas aeruginosa infections. These strategies included:1. Synthesis of a focused compounds library inspired by natural product scaffolds followed by phenotypic screening against Chlamydia trachomatis. (Paper I)(-)-Hopeaphenol is a polyphenol natural product that was identified as an antivirulence agent against Y. pseudotuberculosis and P. aeruginosa. Hopeaphenol core scaffold, 2,3-diaryl-2,3-dihydrobenzofuran, is ubiquitous in polyphenolic phytochemicals. In this thesis, a focused library of forty-eight compounds was synthesized based on 2,3-diarylbenzofuran and 2,3-diaryl-2,3- dihydrobenzofuran. The library was then explored for antibacterial properties in a number of screening assays and resulted in five novel antichlamydial compounds with inhibition potency down to sub-micromolar. The identified molecules also inhibited the growth of different clinical presentations of C. trachomatis, one of the most common sexually transmitted disease worldwide.2. Target-based screening against the P. aeruginosa virulence factor using enzymatic and biophysical assays. (Paper II-IV)P. aeruginosa is a Gram-negative opportunistic pathogen with remarkable antibiotic resistance that is associated with a wide range of clinical infections. An alternative strategy to develop novel and selective antibacterials is to target the bacterial virulence factors, i.e. the ability of the bacteria to promote disease, thus ‘disarming’ the pathogens instead of killing them. P. aeruginosa employs its virulence factor, the type III secretion system (T3SS), to inject toxins (e.g. ExoS) into the eukaryotic cytosol. In one part of this thesis, we utilized enzymatic assay and identified inhibitors against the P. aeruginosa T3S toxin (ExoS). A follow up structure-activity relationship analysis was established and resulted in five (low micromolar) inhibitors of ExoS ADP-ribosylation enzymatic activity. In another part, we used surface plasmon resonance biophysical assay and identified small molecule binders of T3S translocation protein (PcrV). The primary SAR analysis was established and showed the antivirulence properties of these molecules and the potential to expand them further as novel antibacterials.
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| 48. |
- Åkerlund, Thomas, et al.
(författare)
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Stable IgG-antibody levels in patients with mild SARS-CoV-2 infection
- 2021
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Ingår i: Medrxiv. - : Cold Spring Harbor Laboratory.
-
Tidskriftsartikel (refereegranskat)abstract
- More knowledge regarding persistence of antibody response to SARS-CoV-2 infections in the general population with mild symptoms is needed. We measured and compared levels of SARS CoV-2 spike- and nucleocapsid-specific IgG-antibodies in serum samples from 145 laboratory confirmed COVID-19 cases and 324 non-cases. The IgG-antibody levels against the spike protein in cases were stable over the time-period studied (14 to 256 days), while antibody levels against the nucleocapsid protein decreased over time
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| 49. |
- Åkerman, Jonas, 1964, et al.
(författare)
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DN debatt: Beskatta flyget som bilen för att nå klimatmålen
- 2016
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Ingår i: Dagens nyheter.
-
Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Klimatpåverkan från svenskarnas flygresande är nu lika stor som påverkan från allt bilresande i Sverige. Men flygsektorn betalar i dag avsevärt mindre än om den skulle beskattas som vägsektorn. Vi föreslår därför ett paket med klimatdeklaration, passagerarskatt och biobränsleavdrag, skriver tre miljöforskare.
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| 50. |
- Åkerman, Jonas, et al.
(författare)
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Forskare: Så ser vi på alternativen till flygskatt
- 2017
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Ingår i: Dagens Samhälle. - : Dagens samhälle. - 1652-6511.
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Tidskriftsartikel (populärvet., debatt m.m.)abstract
- Sverige och andra länder behöver driva på för att etablera starka internationella styrmedel för att få ner utsläppen från flyget. Detta kommer dock att ta många år. Med tanke på den snabba ökningen av utsläpp krävs därför också temporära styrmedel om Parismålen ska kunna nås.
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