| 1. |
- Alexander, Stephen P. H., et al.
(författare)
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The Concise Guide to PHARMACOLOGY 2023/24: G protein-coupled receptors
- 2023
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Ingår i: BRITISH JOURNAL OF PHARMACOLOGY. - : British pharmacological society. - 0007-1188 .- 1476-5381. ; 180
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Tidskriftsartikel (refereegranskat)abstract
- The Concise Guide to PHARMACOLOGY 2023/24 is the sixth in this series of biennial publications. The Concise Guide provides concise overviews, mostly in tabular format, of the key properties of approximately 1800 drug targets, and about 6000 interactions with about 3900 ligands. There is an emphasis on selective pharmacology (where available), plus links to the open access knowledgebase source of drug targets and their ligands (), which provides more detailed views of target and ligand properties. Although the Concise Guide constitutes almost 500 pages, the material presented is substantially reduced compared to information and links presented on the website. It provides a permanent, citable, point-in-time record that will survive database updates. The full contents of this section can be found at . G protein-coupled receptors are one of the six major pharmacological targets into which the Guide is divided, with the others being: ion channels, nuclear hormone receptors, catalytic receptors, enzymes and transporters. These are presented with nomenclature guidance and summary information on the best available pharmacological tools, alongside key references and suggestions for further reading. The landscape format of the Concise Guide is designed to facilitate comparison of related targets from material contemporary to mid-2023, and supersedes data presented in the 2021/22, 2019/20, 2017/18, 2015/16 and 2013/14 Concise Guides and previous Guides to Receptors and Channels. It is produced in close conjunction with the Nomenclature and Standards Committee of the International Union of Basic and Clinical Pharmacology (NC-IUPHAR), therefore, providing official IUPHAR classification and nomenclature for human drug targets, where appropriate.
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| 2. |
- Christopoulos, Arthur, et al.
(författare)
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THE CONCISE GUIDE TO PHARMACOLOGY 2021/22: G protein-coupled receptors.
- 2021
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Ingår i: British journal of pharmacology. - : Wiley. - 1476-5381 .- 0007-1188. ; 178 Suppl 1
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Forskningsöversikt (refereegranskat)abstract
- The Concise Guide to PHARMACOLOGY 2021/22 is the fifth in this series of biennial publications. The Concise Guide provides concise overviews, mostly in tabular format, of the key properties of nearly 1900 human drug targets with an emphasis on selective pharmacology (where available), plus links to the open access knowledgebase source of drug targets and their ligands (www.guidetopharmacology.org), which provides more detailed views of target and ligand properties. Although the Concise Guide constitutes over 500 pages, the material presented is substantially reduced compared to information and links presented on the website. It provides a permanent, citable, point-in-time record that will survive database updates. The full contents of this section can be found at http://onlinelibrary.wiley.com/doi/bph.15538. G protein-coupled receptors are one of the six major pharmacological targets into which the Guide is divided, with the others being: ion channels, nuclear hormone receptors, catalytic receptors, enzymes and transporters. These are presented with nomenclature guidance and summary information on the best available pharmacological tools, alongside key references and suggestions for further reading. The landscape format of the Concise Guide is designed to facilitate comparison of related targets from material contemporary to mid-2021, and supersedes data presented in the 2019/20, 2017/18, 2015/16 and 2013/14 Concise Guides and previous Guides to Receptors and Channels. It is produced in close conjunction with the Nomenclature and Standards Committee of the International Union of Basic and Clinical Pharmacology (NC-IUPHAR), therefore, providing official IUPHAR classification and nomenclature for human drug targets, where appropriate.
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| 3. |
- Bidlingmaier, Martin, et al.
(författare)
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Reference Intervals for Insulin-like Growth Factor-1 (IGF-1) From Birth to Senescence: Results From a Multicenter Study Using a New Automated Chemiluminescence IGF-1 Immunoassay Conforming to Recent International Recommendations.
- 2014
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Ingår i: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 1945-7197 .- 0021-972X. ; 99:5
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Tidskriftsartikel (refereegranskat)abstract
- Context: Measurement of IGF-1 is a cornerstone in diagnosis and monitoring of GH-related diseases, but considerable discrepancies exist between analytical methods. A recent consensus conference defined criteria for validation of IGF-1 assays and for establishment of normative data. Objectives: Our objectives were development and validation of a novel automated IGF-1 immunoassay (iSYS; Immunodiagnostic Systems) according to international guidelines and establishment of method-specific age- and sex-adjusted reference intervals and analysis of their robustness. Setting and Participants: We conducted a multicenter study with samples from 12 cohorts from the United States, Canada, and Europe including 15ü014 subjects (6697 males and 8317 females, 0-94 years of age). Main Outcome Measures: We measured concentrations of IGF-1 as determined by the IDS iSYS IGF-1 assay. Results: A new IGF-1 assay calibrated against the recommended standard (02/254) and insensitive to the 6 high-affinity IGF binding proteins was developed and rigorously validated. Age- and sex-adjusted reference intervals derived from a uniquely large cohort reflect the age-related pattern of IGF-1 secretion: a decline immediately after birth followed by an increase until a pubertal peak (at 15 years of age). Later in life, values decrease continuously. The impact of gender is small, although across the lifespan, women have lower mean IGF-1 concentrations. Geographical region, sampling setting (community or hospital based), and rigor of exclusion criteria in our large cohort did not affect the reference intervals. Conclusions: Using large cohorts of well-characterized subjects from different centers allowed construction of robust reference ranges for a new automated IGF-1 assay. The strict adherence to recent consensus criteria for IGF-1 assays might facilitate clinical application of the results.
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| 4. |
- Björklund, Martin, 1961-, et al.
(författare)
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Office-cycling while working : An innovative concept to prevent and reduce musculoskeletal pain in office workers - a controlled feasibility study
- 2015
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Konferensbidrag (refereegranskat)abstract
- Background: According to the World Health Organization, WHO, a sedentary lifestyle is the single largest health risk for a number of diseases including musculoskeletal disorders and metabolic diseases. The negative health effects of excessive sitting are not compensated for by shorter bouts of increased physical activity. However, evidence shows that increased physical activity reduces musculoskeletal pain, which is very prevalent in those who are inactive. About 50-70 % of those who work at a computer report musculoskeletal pain and spend on average about 5 hours/day with very low energy metabolism. Work places are therefore an important arena for prevention and intervention by means of reducing sedentary time and increasing physical activity both for general health benefits and effects on the musculoskeletal pain.Purpose: To test the feasibility of office-cycling in an office work place and explore its potential effects on musculoskeletal pain in office workers.Methods: Twenty office workers (ages 27-61, 5 males) with musculoskeletal pain participated in this three-week controlled pilot field study. The intervention group (n=10), had access to an innovative customized cycle ergometer (OfficeBiking®) at their regular office workstation whilst performing their usual work tasks. Offie-cycling was an alternative to sitting/standing by their height adjustable office desk; they were instructed to bike as often as comfortable. The control group (n=10) was instructed to continue to work as usual. The experiences of office-cycling and how it influenced work performance was studied with a questionnaire. Musculoskeletal pain was evaluated using pain drawings and pain ratings and participants' total pain was calculated by adding each individuals' self-reported pain from their three most painful areas (NRS 0-10).Results: Importantly, office-cycling did not reduce self-reported work performance; the majority (9/10) would like daily access; and made suggestions to improve the user-friendliness of the bike. Office-cycling was used regularly (median, 11/15 workdays; median active time 59 min/day IQR 39;91). There was no observed difference regarding either number of self-reported areas of pain (NSAP) or general musculoskeletal pain (GMP) between the intervention group and the control group at baseline. Self-reported GMP decreased in 8 persons in the intervention group which was one more than in the control group (n=7). NSAP decreased in the intervention group (n=7; md -1,0 IQR -2,3;0,0); and the control group (n=5; md -0,5 IQR -1,3;0,3). The difference in total pain (intervention end-baseline) revealed a clinically important change in the intervention group (NRS -2,5, IQR -8,8;4,0) but not in the control group (NRS 0,0 IQR -6,2;2,5).Conclusions: The results suggest that office-cycling is a feasible method for use in work place interventions with some promising results. Future research suggestions are: underlying mechanisms regarding effects of physical activity on pain in parallel with controlled studies in laboratory environments to investigate dose-effects for metabolic expenditure and optimal pain reduction whilst office-cycling.Implications: The results in this feasibility study indicate a promising potential of the innovative office-cycling concept to prevent and reduce musculoskeletal pain in sedentary office workers.
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| 5. |
- Björkman, Lena, 1965, et al.
(författare)
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The Neutrophil Response Induced by an Agonist for Free Fatty Acid Receptor 2 (GPR43) Is Primed by Tumor Necrosis Factor Alpha and by Receptor Uncoupling from the Cytoskeleton but Attenuated by Tissue Recruitment
- 2016
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Ingår i: Molecular and Cellular Biology. - : Informa UK Limited. - 0270-7306 .- 1098-5549. ; 36:20, s. 2583-2595
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Tidskriftsartikel (refereegranskat)abstract
- Ligands with improved potency and selectivity for free fatty acid receptor 2 (FFA2R) have become available, and we here characterize the neutrophil responses induced by one such agonist (Cmp1) and one antagonist (CATPB). Cmp1 triggered an increase in the cytosolic concentration of Ca2+, and the neutrophils were then desensitized to Cmp1 and to acetate, a naturally occurring FFA2R agonist. The antagonist CATPB selectively inhibited responses induced by Cmp1 or acetate. The activated FFA2R induced superoxide anion secretion at a low level in naive blood neutrophils. This response was largely increased by tumor necrosis factor alpha (TNF-alpha) in a process associated with a recruitment of easily mobilizable granules, but neutrophils recruited to an aseptic inflammation in vivo were nonresponding. Superoxide production induced by Cmp1 was increased in latrunculin A-treated neutrophils, but no reactivation of desensitized FFA2R was induced by this drug, suggesting that the cytoskeleton is not directly involved in terminating the response. The functional and regulatory differences between the receptors that recognize short-chain fatty acids and formylated peptides, respectively, imply different roles of these receptors in the orchestration of inflammation and confirm the usefulness of a selective FFA2R agonist and antagonist as tools for the exploration of the precise role of the FFA2R.
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| 6. |
- Brännström, Inger, 1945-, et al.
(författare)
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Co-operation, participation and conflicts faced in public health : lessons learned from a long-term prevention programme in Sweden
- 1994
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Ingår i: Health Education Research. - : Oxford University Press. - 0268-1153 .- 1465-3648. ; 9:3, s. 317-329
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Tidskriftsartikel (refereegranskat)abstract
- A comprehensive community-based programme for prevention of cardiovascular diseases (CVD) and diabetes was established in 1985 in a small municipality in northern Sweden. A cross-sectional survey to the general public was performed and semi-structured open-ended interviews were taken of actors at different levels. Notes from official records were also included in the study. The aim was to describe and discuss some factors that promote or constrain community participation in health programmes. The results generally confirmed that the right of definition concerning the health programme mainly remained with the health professionals. Community participation was mainly defined by the actors based on the medical and health planning approach and, thereby, as a means to transform health policy plans into reality by transmitting health knowledge and increasing consciousness among the citizens of the need for changing lifestyles. However, participation as a means of identifying problems and demonstrating power relationships and as elements in promoting local democracy was hardly represented among the actors at all. Overall, the CVD health programme was characterized by consensus between the actors. Despite this, debates and arguments about interpretations, social interests, personal conflicts and ideological constraints were observed. However, a majority of the public wanted the CVD preventive programme to continue.
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| 7. |
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| 8. |
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| 9. |
- Dahlgren, Martin
(författare)
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Optimal sale strategies in illiquid markets
- 2005
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Ingår i: Mathematical Methods of Operations Research. - : Springer Science and Business Media LLC. - 1432-2994 .- 1432-5217. ; 61:2, s. 173-190
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Tidskriftsartikel (refereegranskat)abstract
- The value of a position in a risky asset when optimally sold in an illiquid market is considered. The optimization problem is described as a stochastic impulse control problem, and it is shown that it is related to solving a system of quasi-variational inequalities. Existence of a solution to these inequalities are proved. A numerical implementation of the valuation algorithm is discussed and two numerical examples are presented. Further, two examples where the stochastic impulse control problem can be reduced to deterministic optimization problems are also given.
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| 10. |
- Dahlgren, Malin, et al.
(författare)
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Preexisting Somatic Mutations of Estrogen Receptor Alpha (ESR1) in Early-Stage Primary Breast Cancer
- 2021
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Ingår i: JNCI Cancer Spectrum. - : Oxford University Press (OUP). - 2515-5091. ; 5:2
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Tidskriftsartikel (refereegranskat)abstract
- More than three-quarters of primary breast cancers are positive for estrogen receptor alpha (ER; encoded by the gene ESR1), the most important factor for directing anti-estrogenic endocrine therapy (ET). Recently, mutations in ESR1 were identified as acquired mechanisms of resistance to ET, found in 12% to 55% of metastatic breast cancers treated previously with ET. We analyzed 3217 population-based invasive primary (nonmetastatic) breast cancers (within the SCAN-B study, ClinicalTrials.gov NCT02306096), sampled from initial diagnosis prior to any treatment, for the presence of ESR1 mutations using RNA sequencing. Mutations were verified by droplet digital polymerase chain reaction on tumor and normal DNA. Patient outcomes were analyzed using Kaplan-Meier estimation and a series of 2-factor Cox regression multivariable analyses. We identified ESR1 resistance mutations in 30 tumors (0.9%), of which 29 were ER positive (1.1%). In ET-treated disease, presence of ESR1 mutation was associated with poor relapse-free survival and overall survival (2-sided log-rank test P < .001 and P = .008, respectively), with hazard ratios of 3.00 (95% confidence interval = 1.56 to 5.88) and 2.51 (95% confidence interval = 1.24 to 5.07), respectively, which remained statistically significant when adjusted for other prognostic factors. These population-based results indicate that ESR1 mutations at diagnosis of primary breast cancer occur in about 1% of women and identify for the first time in the adjuvant setting that such preexisting mutations are associated to eventual resistance to standard hormone therapy. If replicated, tumor ESR1 screening should be considered in ER-positive primary breast cancer, and for patients with mutated disease, ER degraders such as fulvestrant or other therapeutic options may be considered as more appropriate.
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