Publications by authors named "C V Dahlgren"

310 Publications

THE CONCISE GUIDE TO PHARMACOLOGY 2021/22: G protein-coupled receptors.

Br J Pharmacol 2021 Oct;178 Suppl 1:S27-S156

University of Córdoba, Córdoba, Spain.

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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http://dx.doi.org/10.1111/bph.15538DOI Listing
October 2021

Multiple ligand recognition sites in free fatty acid receptor 2 (FFA2R) direct distinct neutrophil activation patterns.

Biochem Pharmacol 2021 Sep 6;193:114762. Epub 2021 Sep 6.

Department of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Sweden. Electronic address:

The allosteric modulating free fatty acid receptor 2 ligands Cmp58 and AZ1729, increased the activity induced by orthosteric receptor agonists mediating a rise in intracellular calcium ions and activation of the neutrophil NADPH-oxidase. Together, the two modulators triggered an orthosteric-agonist-independent activation of the oxidase without any rise in the concentration of intracellular calcium ions. In this study, structurally diverse compounds presumed to be ligands for free fatty acid receptor 2 were used to gain additional insights into receptor-modulation/signaling. We identified two molecules that activate neutrophils on their own and we classified one as allosteric agonist and the other as orthosteric agonist. Ten compounds were classified as allosteric FFA2R modulators. Of these, one activated neutrophils when combined with AZ1729; the nine remaining compounds activated neutrophils solely when combined with Cmp58. The activation signals were primarily biased when stimulated by two allosteric modulators interacting with different binding sites, such that two complementary modulators together triggered an activation of the NADPH-oxidase but no increase in the intracellular concentration of calcium ions. No neutrophil activation was induced when allosteric receptor modulators suggested to be recognized by the same binding site were combined, results in agreement with our proposed model for activation, in which the receptor has two different sites that selectively bind allosteric modulators. The down-stream signaling mediated by cross-sensitizing allosteric receptor modulators, occurring independent of any orthosteric agonist, represent a new mechanism for activation of the neutrophil NADPH oxidase.
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http://dx.doi.org/10.1016/j.bcp.2021.114762DOI Listing
September 2021

Experimental assessment of inter-centre variation in stopping-power and range prediction in particle therapy.

Radiother Oncol 2021 Jul 27;163:7-13. Epub 2021 Jul 27.

OncoRay - National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Helmholtz-Zentrum Dresden - Rossendorf, Dresden, Germany; Helmholtz-Zentrum Dresden - Rossendorf, Institute of Radiooncology - OncoRay, Dresden, Germany; Department of Radiotherapy and Radiation Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Germany; German Cancer Consortium (DKTK), partner site Dresden, and German Cancer Research Center (DKFZ), Heidelberg, Germany.

Purpose: Experimental assessment of inter-centre variation and absolute accuracy of stopping-power-ratio (SPR) prediction within 17 particle therapy centres of the European Particle Therapy Network.

Material And Methods: A head and body phantom with seventeen tissue-equivalent materials were scanned consecutively at the participating centres using their individual clinical CT scan protocol and translated into SPR with their in-house CT-number-to-SPR conversion. Inter-centre variation and absolute accuracy in SPR prediction were quantified for three tissue groups: lung, soft tissues and bones. The integral effect on range prediction for typical clinical beams traversing different tissues was determined for representative beam paths for the treatment of primary brain tumours as well as lung and prostate cancer.

Results: An inter-centre variation in SPR prediction (2σ) of 8.7%, 6.3% and 1.5% relative to water was determined for bone, lung and soft-tissue surrogates in the head setup, respectively. Slightly smaller variations were observed in the body phantom (6.2%, 3.1%, 1.3%). This translated into inter-centre variation of integral range prediction (2σ) of 2.9%, 2.6% and 1.3% for typical beam paths of prostate-, lung- and primary brain-tumour treatments, respectively. The absolute error in range exceeded 2% in every fourth participating centre. The consideration of beam hardening and the execution of an independent HLUT validation had a positive effect, on average.

Conclusion: The large inter-centre variations in SPR and range prediction justify the currently clinically used margins accounting for range uncertainty, which are of the same magnitude as the inter-centre variation. This study underlines the necessity of higher standardisation in CT-number-to-SPR conversion.
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http://dx.doi.org/10.1016/j.radonc.2021.07.019DOI Listing
July 2021

Determinants for use of direct-to-consumer telemedicine consultations in primary healthcare-a registry based total population study from Stockholm, Sweden.

BMC Fam Pract 2021 06 26;22(1):133. Epub 2021 Jun 26.

Department of Learning, Informatics, Management and Ethics, Karolinska Institutet, Stockholm, Sweden.

Background: In recent years, telemedicine consultations have evolved as a new form of providing primary healthcare. Telemedicine options can provide benefits to patients in terms of access, reduced travel time and no risk of disease spreading. However, concerns have been raised that access is not equally distributed in the population, which could lead to increased inequality in health. The aim of this paper is to explore the determinants for use of direct-to-consumer (DTC) telemedicine consultations in a setting where telemedicine is included in the publicly funded healthcare system.

Methods: To investigate factors associated with the use of DTC telemedicine, a database was constructed by linking national and regional registries covering the entire population of Stockholm, Sweden (N = 2.3 million). Logistic regressions were applied to explore the determinants for utilization in 2018. As comparators, face-to-face physician consultations in primary healthcare were included in the study, as well as digi-physical physician consultations, i.e., telemedicine consultations offered by traditional primary healthcare providers also offering face-to-face visits, and telephone consultations by nurses.

Results: The determinants for use of DTC telemedicine differed substantially from face-to-face visits but also to some extent from the other telemedicine options. For the DTC telemedicine consultations, the factors associated with higher probability of utilization were younger age, higher educational attainment, higher income and being born in Sweden. In contrast, the main determinants for use of face-to-face visits were higher age, lower educational background and being born outside of Sweden.

Conclusion: The use of DTC telemedicine is determined by factors that are generally not associated with greater healthcare need and the distribution raises some concerns about the equity implications. Policy makers aiming to increase the level of telemedicine consultations in healthcare should consider measures to promote access for elderly and individuals born outside of Sweden to ensure that all groups have access to healthcare services according to their needs.
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http://dx.doi.org/10.1186/s12875-021-01481-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8233176PMC
June 2021

Produce Neutrophil Specific Chemoattractants Including Short Chain Fatty Acids.

Front Cell Infect Microbiol 2020 19;10:620681. Epub 2021 Jan 19.

Department of Oral Microbiology and Immunology, Institute of Odontology, The Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.

Neutrophil migration from blood to tissue-residing microbes is governed by a series of chemoattractant gradients of both endogenous and microbial origin. Periodontal disease is characterized by neutrophil accumulation in the gingival pocket, recruited by the subgingival biofilm consisting mainly of gram-negative, anaerobic and proteolytic species such as . The fact that neutrophils are the dominating cell type in the gingival pocket suggests that neutrophil-specific chemoattractants are released by subgingival bacteria, but characterization of chemoattractants released by subgingival biofilm species remains incomplete. In the present study we characterized small (< 3 kDa) soluble chemoattractants released by growing , and show that these are selective for neutrophils. Most neutrophil chemoattractant receptors are expressed also by mononuclear phagocytes, the free fatty acid receptor 2 (FFAR2) being an exception. In agreement with the selective neutrophil recruitment, the chemotactic activity found in supernatants was mediated in part by a mixture of short chain fatty acids (SCFAs) that are recognized by FFAR2, and other leukocytes (including monocytes) did not respond to SCFA stimulation. Although SCFAs, produced by bacterial fermentation of dietary fiber in the gut, has previously been shown to utilize FFAR2, our data demonstrate that the pronounced proteolytic metabolism employed by (and likely also other subgingival biofilm bacteria associated with periodontal diseases) may result in the generation of SCFAs that attract neutrophils to the gingival pocket. This finding highlights the interaction between SCFAs and FFAR2 in the context of colonization during periodontal disease, but may also have implications for other inflammatory pathologies involving proteolytic bacteria.
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http://dx.doi.org/10.3389/fcimb.2020.620681DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7851090PMC
June 2021
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