| 1. |
- Alexander, Stephen P. H., et al.
(author)
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The Concise Guide to PHARMACOLOGY 2023/24: G protein-coupled receptors
- 2023
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In: BRITISH JOURNAL OF PHARMACOLOGY. - : British pharmacological society. - 0007-1188 .- 1476-5381. ; 180
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Journal article (peer-reviewed)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.
(author)
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THE CONCISE GUIDE TO PHARMACOLOGY 2021/22: G protein-coupled receptors.
- 2021
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In: British journal of pharmacology. - : Wiley. - 1476-5381 .- 0007-1188. ; 178 Suppl 1
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Research review (peer-reviewed)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. |
- Docherty, Anna R, et al.
(author)
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GWAS Meta-Analysis of Suicide Attempt: Identification of 12 Genome-Wide Significant Loci and Implication of Genetic Risks for Specific Health Factors.
- 2023
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In: The American journal of psychiatry. - : American Psychiatric Association Publishing. - 1535-7228 .- 0002-953X. ; 180:10, s. 723-738
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Journal article (peer-reviewed)abstract
- Suicidal behavior is heritable and is a major cause of death worldwide. Two large-scale genome-wide association studies (GWASs) recently discovered and cross-validated genome-wide significant (GWS) loci for suicide attempt (SA). The present study leveraged the genetic cohorts from both studies to conduct the largest GWAS meta-analysis of SA to date. Multi-ancestry and admixture-specific meta-analyses were conducted within groups of significant African, East Asian, and European ancestry admixtures.This study comprised 22 cohorts, including 43,871 SA cases and 915,025 ancestry-matched controls. Analytical methods across multi-ancestry and individual ancestry admixtures included inverse variance-weighted fixed-effects meta-analyses, followed by gene, gene-set, tissue-set, and drug-target enrichment, as well as summary-data-based Mendelian randomization with brain expression quantitative trait loci data, phenome-wide genetic correlation, and genetic causal proportion analyses.Multi-ancestry and European ancestry admixture GWAS meta-analyses identified 12 risk loci at p values <5×10-8. These loci were mostly intergenic and implicated DRD2, SLC6A9, FURIN, NLGN1, SOX5, PDE4B, and CACNG2. The multi-ancestry SNP-based heritability estimate of SA was 5.7% on the liability scale (SE=0.003, p=5.7×10-80). Significant brain tissue gene expression and drug set enrichment were observed. There was shared genetic variation of SA with attention deficit hyperactivity disorder, smoking, and risk tolerance after conditioning SA on both major depressive disorder and posttraumatic stress disorder. Genetic causal proportion analyses implicated shared genetic risk for specific health factors.This multi-ancestry analysis of suicide attempt identified several loci contributing to risk and establishes significant shared genetic covariation with clinical phenotypes. These findings provide insight into genetic factors associated with suicide attempt across ancestry admixture populations, in veteran and civilian populations, and in attempt versus death.
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| 4. |
- Mörtberg, Josefin, et al.
(author)
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Prognostic importance of biomarkers associated with haemostatic, vascular and endothelial disturbances in acute coronary syndrome patients in relation to kidney function
- 2023
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In: International Journal of Cardiology. - : Elsevier BV. - 0167-5273 .- 1874-1754. ; 373, s. 64-71
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Journal article (peer-reviewed)abstract
- BACKGROUND: Patients with kidney failure have a high risk for cardiovascular events. We aimed to evaluate the prognostic importance of selected biomarkers related to haemostasis, endothelial function, and vascular regulation in patients with acute coronary syndrome (ACS), and to study whether this association differed in patients with renal dysfunction.METHODS: Plasma was collected in 1370 ACS patients included between 2008 and 2015. Biomarkers were analysed using a Proximity Extension Assay and a Multiple Reaction Monitoring mass spectrometry assay. To reduce multiplicity, biomarkers correlating with eGFR were selected a priori among 36 plasma biomarkers reflecting endothelial and vascular function, and haemostasis. Adjusted Cox regression were used to study their association with the composite outcome of myocardial infarction, ischemic stroke, heart failure or death. Interaction with eGFR strata above or below 60 ml/min/1.73 m 2 was tested. RESULTS: Tissue factor, proteinase-activated receptor, soluble urokinase plasminogen activator surface receptor (suPAR), thrombomodulin, adrenomedullin, renin, and angiotensinogen correlated inversely with eGFR and were selected for the Cox regression. Mean follow-up was 5.2 years during which 428 events occurred. Adrenomedullin, suPAR, and renin were independently associated with the composite outcome. Adrenomedullin showed interaction with eGFR strata (p = 0.010) and was associated with increased risk (HR 1.88; CI 1.44-2.45) only in patients with eGFR ≥60 ml/min/ 1.73 m 2. CONCLUSIONS: Adrenomedullin, suPAR, and renin were associated with the composite outcome in all. Adrenomedullin, involved in endothelial protection, showed a significant interaction with renal function and outcome, and was associated with the composite outcome only in patients with preserved kidney function.
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| 5. |
- Olsson, Jenny, et al.
(author)
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Expression of neutrophil SOD2 is reduced after lipopolysaccharide stimulation : A potential cause of neutrophil dysfunction in chronic kidney disease
- 2011
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In: Nephrology Dialysis Transplantation. - : Oxford University Press (OUP). - 0931-0509 .- 1460-2385. ; 26:7, s. 2195-2201
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Journal article (peer-reviewed)abstract
- Background. Neutrophils from patients with chronic kidney disease (CKD) are dysfunctional and thus a contributing factor to the risk of infections. The mechanisms for leucocyte dysfunction in CKD are not fully understood. It is known that lipopolysaccharide (LPS) activates transcription of several genes encoding proinflammatory cytokines. We therefore aimed to study the effect of LPS on neutrophil expression of genes related to the inflammatory response to address the hypothesis that LPS-induced gene transcriptions are altered in CKD patients.Methods. We analysed gene expression of LPS-stimulated neutrophils from 30 patients with CKD and 15 healthy controls. Superoxide dismutase-2 (SOD2), IL1A, IL-1R1, IL-1R2 and IL8RA gene expression from both neutrophils and differentiated HL60 cells were measured by quantitative polymerase chain reaction. Differentiated HL60 cells were stimulated with phorbol-12-myristate-7- acetate (PMA) after inhibition of SOD2 by small interfering RNA followed by respiratory burst assessment using flow cytometry.Results. LPS stimulation induced a significant mobilization of CD11b on neutrophils from CKD and healthy controls. Upregulation of SOD2, IL1A, IL-1R1 and IL-1R2 gene expression in neutrophils from healthy controls after LPS stimulation was contrasted by no change in gene transcription (IL-1R1 and IL-1R2) or even a downregulation in patients with CKD (SOD2 and IL1A). Inhibition of SOD2 reduced the PMA-induced respiratory burst and IL1A, IL-1R1, IL-1R2 and IL8RA gene expression in neutrophil-differentiated HL60 cells.Conclusions. Because of the critical role of SOD2 in the generation of hydrogen peroxide during phagocytosis, downregulation of SOD2 gene expression after LPS stimulation in neutrophils from patients with CKD indicates a potential mechanism for neutrophil dysfunction and cytokine dysregulation in these patients.
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| 6. |
- Aljadi, Zenib, et al.
(author)
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Activation of Basophils Is a New and Sensitive Marker of Biocompatibility in Hemodialysis
- 2014
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In: Artificial Organs. - : Wiley. - 0160-564X .- 1525-1594. ; 38:11, s. 945-953
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Journal article (peer-reviewed)abstract
- The hemodialysis procedure involves contact between peripheral blood and the surface of dialyzer membranes, which may lead to alterations in the pathways of innate and adaptive immunity. We aimed to study the effect of blood-membrane interaction on human peripheral basophils and neutrophils in hemodialysis with high- and low-permeability polysulfone dialyzers. The surface expression of CD203c (basophil selection marker) and CD63 (activation marker) after activation by the bacterial peptide formyl-methionyl-leucyl-phenylalanine (fMLP) or anti-Fc epsilon receptor I (Fc epsilon RI) antibody and the absolute number of basophils was investigated before and after hemodialysis with each of the dialyzers. Moreover, the expression on neutrophils of CD11b, the CD11b active epitope, and CD88 was analyzed in the same groups of individuals. The expression of CD63 in basophils following activation by fMLP was significantly higher in the patient group compared with that in healthy controls, but no differences were observed after activation by anti-Fc epsilon RI. During the hemodialysis procedure, the low-flux membrane induced up-regulation of CD63 expression on basophils, while passage through the high-flux membrane did not significantly alter the responsiveness. In addition, the absolute number of basophils was unchanged after hemodialysis with either of the dialyzers and compared with healthy controls. We found no significant differences in the expression of the neutrophil activation markers (CD11b, the active epitope of CD11b, and CD88) comparing the two different dialyzers before and after dialysis and healthy controls. Together, these findings suggest that alterations in basophil activity may be a useful marker of membrane bioincompatibility in hemodialysis.
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| 7. |
- Aljadi, Zenib, et al.
(author)
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Altered basophil function in patients with chronic kidney disease on hemodialysis
- 2017
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In: Clinical Nephrology. - : DUSTRI-VERLAG DR KARL FEISTLE. - 0301-0430. ; 88:2, s. 86-96
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Journal article (peer-reviewed)abstract
- Aims: Chronic kidney disease (CKD) leads to impairment of immune cell function. Given the potential role of basophils in the pathogenesis of CKD, we aimed to study the basophil responsiveness towards microbial antigen exposure, judged as adhesion molecule expression and degranulation, in CKD patients on hemodialysis. Materials and methods: We selected markers linked to two crucial biological phases: the transmigration and degranulation processes, respectively. For the transmigration process, we selected the adhesion molecules CD11b, active CD11b epitope, and CD62L and for the degranulation process CD203c (piecemeal degranulation marker), CD63 (degranulation marker), and CD300a (inhibitory marker of degranulation). We measured basophil responsiveness after stimulation of different activation pathways in basophils using lipopolysaccharide (LPS), peptidoglycan (PGN), formyl-methyinoyl-leucyl-phenylalanine (fMLP), and anti-FceRI-ab. Results: The expression of CD63 in basophils following activation by fMLP was significantly higher in the patient group compared to matched healthy controls, but no differences were observed after activation by anti-Fc.RI. CD300a expression was significantly higher in patients following activation by fMLP and anti-Fc.RI, and the active epitope CD11b expression was significantly higher in patients after LPS activation. In addition, we found that CD62L was not shed from the cell surface after activation with LPS and fMLP. A slight downregulation was noted after activation with anti-Fc.RI in healthy controls. Conclusion: Together, these data demonstrate that basophil functions related to adhesion and degranulation are altered in CKD patients on hemodialysis, which indicates a potential role for the basophil in the pathogenesis of complications related to infections.
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| 8. |
- Asp, Anna M., et al.
(author)
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Cardiac remodelling and functional alterations in mild-to-moderate renal dysfunction: Comparison with healthy subjects
- 2015
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In: Clinical Physiology and Functional Imaging. - : Wiley. - 1475-0961 .- 1475-097X. ; 35:3, s. 223-230
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Journal article (peer-reviewed)abstract
- © 2014 The Authors. Introduction: Left ventricular (LV) hypertrophy (LVH) and reduced LV function correlate with poor prognosis in patients with chronic kidney disease (CKD). Our aim is to investigate whether mild-to-moderate CKD is associated with cardiac abnormalities. Methods: Echocardiography, including tissue Doppler imaging, was performed in 103 patients with CKD at stages 2-3 and 4-5, and in 53 healthy controls. The systolic (s′) and diastolic myocardial velocity (e′), and the transmitral diastolic flow velocity (E) were measured, and E/e′ was calculated. Results: Patients with chronic kidney disease had higher mean E/e′ than controls (mean E/e′: controls 5·00 ± 1·23 versus CKD 4-5 6·36 ± 1·71, P < 0·001 and versus CKD 2-3 5·69 ± 1·47, P = 0·05), indicating altered diastolic function in the patients. The CKD groups showed lower longitudinal systolic function than controls, as assessed by atrio-ventricular plane displacement and s′ (mean s′: controls 11·5 ± 1·9 cm s < sup > -1 < /sup > versus CKD 4-5 10·4 ± 2·1 cm s < sup > -1 < /sup > , P = 0·03 and versus CKD 2-3 10·4 ± 2·1 cm s < sup > -1 < /sup > , P = 0·02). The prevalence of LVH was higher in patients with CKD than in controls (controls 13% versus CKD 4-5 37%, P = 0·006 and versus CKD 2-3 30%, P = 0·03). Conclusion: Alterations in systolic and diastolic myocardial function can be seen in mild-to-moderate CKD compared with controls, indicating that cardiac involvement starts early in CKD, which may be a precursor of premature cardiac morbidity.
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| 9. |
- Axelsson, Lena, et al.
(author)
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End of life of patients treated with haemodialysis as narrated by their close relatives
- 2015
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In: Scandinavian Journal of Caring Sciences. - : Wiley. - 0283-9318 .- 1471-6712. ; 29:4, s. 776-784
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Journal article (peer-reviewed)abstract
- AIM: The study aimed to describe end of life for patients treated with maintenance haemodialysis as narrated by their close relatives.INTRODUCTION: Many patients undergoing haemodialysis are older, have several comorbidities and underestimated symptoms and are in their last year of life. To improve care, we need to know more about their end-of-life situation.DESIGN: Qualitative and descriptive.METHODS: Qualitative retrospective interviews were conducted with 14 close relatives of deceased haemodialysis patients (3-13 months after death). Data were analysed using qualitative content analysis. The study is ethically approved.FINDINGS: In the last months, a gradual deterioration in health with acute episodes necessitating hospital admissions was described. This involved diminishing living space and expressions of dejection, but also of joy. Three patterns emerged in the last weeks: uncertain anticipation of death as life fades away; awaiting death after haemodialysis withdrawal; and sudden but not unexpected death following intensive care. Findings show complexities of decisions on haemodialysis withdrawal.CONCLUSIONS: Different end-of-life patterns all involved increasingly complex care needs and existential issues. Findings show a need for earlier care planning. The identification of organisational factors to facilitate continuity and whole person care to meet these patients' specific care needs with their complex symptom burdens and comorbidities is needed. Findings indicate the need for integration of a palliative care approach in the treatment of patients in haemodialysis care.
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| 10. |
- Axelsson, Lena
(author)
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Living with haemodialysis close to death - patients' and close relatives' experiences
- 2013
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Doctoral thesis (other academic/artistic)abstract
- The overall aim of this thesis is to generate understanding and knowledge a bout the experiences of patients living with haemodialysis, and their close relati ves, near the end of life. In studies I and II we conducted a series of 31 qualitative interviews over a period of 12 months with 8 severely ill patients (aged 66–87) treated with haemodialysis. For study I the text of the interviews was analysed using phenomenological hermeneutics to describe and to el ucidate the meanings of being severely ill living with haemodialysis when nearing end of life. For study II the text was analysed using qualitative content analysis to describe inner thoughts and feelings relating to death and dying of these patients. For studies III and IV, we conducted 14 retrospective qualitative interviews with close relatives of deceased patients treated with haemodialysis about th eir experiences during end of the patient’s life. For paper III the interview text was analysed usi ng phenomenological hermeneu tics to describe and elucidate the meanings of being a close relative at the end of life of a severely ill family member treated with maintenance haemodialysis. For paper IV the text was analysed using qualitative content analysis to describe end of life for the patients from the perspective of their close relatives. The findings of study I suggest that being severely i ll and living with haemodialysis near the end of life means living with suffering from a deteriorating body, a high symptom burden, and dependence on advanced medical technology, simultaneously with r econciliation and well-being. The meanings of living with illness and dialysis are intertwined with the meanings of being old. Study II shows that thoughts and feelings about deat h and dying are significant and complex for those living with haemodialysis as they approach the end of life. Patients experience a multifaceted presence of death. Their awareness of approaching death may include their repressing of thoughts of death, not as denial, but to allow them to focus on living as fully as possible the time they have left. Study III shows that close relatives strive to maintain balance and well-being for themselves and for the patient, which we interpreted as their striving to regain balance, and inner equilibrium in their changed and challenged rhythm of life. Study IV shows that after gradual deterioration and increasing care needs, older patients in haemodialysis care with co-morbidities follow three different main paths at the end of life: uncertain anticipation of death; awaiting death after dialysis withdrawal; and sudden but not unexpected death. The ends of their lives are marked by complex symptoms and existential issues related to haemodialysis treatment and withdrawal, and their uncertainty of what to expect at the end of life suggests the need for increased continuity and coordination of whole person care. Both patients and their close relatives are often alone with their existential thoughts. In their complex lifeworlds, intertwined meanings of living with illness and maintenance of life with haemodialysis treatment near the end of life show that patients live in a borderland of living-dying that is shared by the close relative. Patients and close relatives focus on living when death is close but uncertain, with severe illness and the maintenance of life through advanced technology. Integrating the philosophy of palliative care (with a focus on symptom relief, team work, communication, relationships, and support of family members) into dialysis care, may support health care professionals in haemodialysis units and other re nal contexts, to improve the care of severely ill patients, both earlier in their illness and as they approach the end of their lives.
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