| 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. |
- Jacobson, Dan
(författare)
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Cerebral palsy : studies on health and social outcomes in young adulthood, and on treatments for spasticity and pain
- 2020
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Cerebral palsy (CP) is a permanent disorder caused by a non-progressive brain injury or malformation that has occurred early in the development of the child’s brain. The disorder is characterized by dysfunction of movement and posture, with frequent but variable occurrences of other dysfunctions in cognition, perception, sensation, communication, as well as of epilepsy, and pain. The movement dysfunctions are often what is most apparent for an outside observer and interventions have traditionally focused primarily on movement. Spasticity, a type of abnormal contraction of muscles, is common in CP and an aspect of movement that is often targeted for treatment. As CP is a life-long disorder it is important to understand the long-term effects of treatments, especially if they are performed early in life. It is also important to understand how the disorder and the consequences of the disorder evolve ‘long-term’ as the individual grows up. Our knowledge of CP after childhood has been limited. Concerns have been raised on the topics of integration into society for adults with CP, and on some emerging health issues; especially a high prevalence of chronic pain. Understanding these issues and finding ways to manage them is a priority. This thesis focuses on the health and social situation of individuals with CP right after childhood, and on specific treatments for spasticity and pain. This was done using a few separate methods. Health and social situation were investigated cross-sectionally in 20-22- year-old young adults with CP. The long-term effects of the spasticity-reducing neurosurgical procedure selective dorsal rhizotomy (SDR) were investigated using a consecutive case series. And botulinum toxin-A (BoNT-A) was tested as a treatment for chronic musclerelated pain in adults with CP by means of a randomized, placebo-controlled, double-blinded clinical trial. It was found that most young adults with CP still lived in their parental home; more so than in the general population. A majority of those without an intellectual disability had an occupation, but the risk of having no occupation at all was increased. Communication function classification level (CFCS), and intellectual disability were major determinants of the social outcomes, while gross motor function classification level (GMFCS) was not. The overall health-related quality of life (HRQoL) of young adults with CP was comparable to population norms. There were, however, significant sub-group differences across different levels of gross motor function. Pain and fatigue were prevalent across all levels of functioning. The SDR procedure was effective in the long term in reducing spasticity, but this did not prevent contracture development, nor did it seem to improve functioning. Finally, BoNT-A was not superior to placebo in reducing pain in adults with CP at six weeks after treatment. Pain intensity did, however, trend downwards in the BoNT-A group at the last follow-up, suggesting that trials of longer duration are warranted.
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| 3. |
- Jacobson, Dan N O, et al.
(författare)
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A First Clinical Trial on Botulinum Toxin-A for Chronic Muscle-Related Pain in Cerebral Palsy
- 2021
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Ingår i: Frontiers in Neurology. - : Frontiers Media S.A.. - 1664-2295. ; 12
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To test if botulinum toxin-A (BoNT-A) is effective in reducing chronic muscle-related pain in adults with spastic cerebral palsy (CP), as compared to placebo.Design: A single-center, double-blind, parallel, randomized placebo-controlled trial. The design included an interim analysis to allow for confirmatory analysis, as well as pilot study outcomes.Setting: Tertiary university hospital.Participants: Adults with spastic CP and chronic pain associated with spastic muscle(s).Intervention: Treatment was one session of electromyographically guided intramuscular injections of either BoNT-A or placebo normosaline.Main Study Outcomes: The primary outcome was the proportion who achieved a reduction of pain intensity of two or more steps on the Numerical Rating Scale 6 weeks after treatment.Results: Fifty individuals were screened for eligibility, of whom 16 were included (10 female, 6 male, mean age = 32 years, SD = 13.3 years). The randomization yielded eight participants per treatment arm, and all completed the study as randomized. The study was stopped at the interim analysis due to a low probability, under a preset threshold, of a positive primary outcome. Four individuals were treatment responders in the BoNT-A group for the primary outcome compared to five responders in the placebo group (p = 1.000). Adverse events were mild to moderate. In exploratory analysis, the BoNT-A group had a trend of continuing reduction of pain at the last follow-up, after the primary endpoint.Conclusions: This study did not find evidence that BoNT-A was superior to placebo at the desired effect size (number needed to treat of 2.5) at 6 weeks after treatment. Trial registration: ClinicalTrials.gov: NCT02434549
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| 4. |
- Jacobson, Dan N O, et al.
(författare)
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Health-related quality of life, pain, and fatigue in young adults with cerebral palsy
- 2020
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Ingår i: Developmental Medicine & Child Neurology. - : Wiley. - 0012-1622 .- 1469-8749. ; 62:3, s. 372-378
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Tidskriftsartikel (refereegranskat)abstract
- AIM: To describe health-related quality of life (HRQoL), pain, fatigue, and other health variables in young adults with cerebral palsy (CP), and to explore associations with the Gross Motor Function Classification System - Expanded and Revised (GMFCS-ER) and physical activity.METHOD: This was a cross-sectional study of 61 young adults at a mean age of 21 years 2 months (standard deviation 8mo, range 20-22y) with CP, from a geographically defined area. Data collection included: Short Form 36 version 2 for HRQoL, Brief Pain Inventory - Short Form, Fatigue Severity Scale, level of physical activity, medical history, and physical examination.RESULTS: Overall HRQoL equalled that of population norms; however self-reported physical health was lower in GMFCS-ER levels III to V compared to GMFCS-ER levels I to II. Self-reported mental health was, inversely, lower in GMFCS-ER levels I to II compared to GMFCS-ER levels III to V. Pain prevalence was 49%, and pain was present across all GMFCS-ER levels. Fatigue, as well as sleep problems, had 41% prevalence, with fatigue severity decreasing with increasing level of physical activity.INTERPRETATION: General HRQoL in young adults with CP was comparable to population norms. Pain and fatigue are important to address in high motor-functioning individuals also. Physical activity could be a possible protective factor against fatigue.WHAT THIS PAPER ADDS:Health-related quality of life in young adults with cerebral palsy (CP) was comparable to population norms.Pain, fatigue, and sleep problems occurred at all Gross Motor Function Classification System levels.There is a possible protective effect of physical activity on fatigue.
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| 5. |
- Leibovitzh, Haim, et al.
(författare)
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Immune response and barrier dysfunction-related proteomic signatures in preclinical phase of Crohn's disease highlight earliest events of pathogenesis
- 2023
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Ingår i: Gut. - : BMJ Publishing Group Ltd. - 0017-5749 .- 1468-3288. ; 72:8, s. 1462-1471
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: The measure of serum proteome in the preclinical state of Crohn's disease (CD) may provide insight into biological pathways involved in CD pathogenesis. We aimed to assess associations of serum proteins with future CD onset and with other biomarkers predicting CD risk in a healthy at-risk cohort.DESIGN: In a nested case-control study within the Crohn's and Colitis Canada Genetics Environment Microbial Project (CCC-GEM) cohort, which prospectively follows healthy first-degree relatives (FDRs), subjects who developed CD (n=71) were matched with four FDRs remaining healthy (n=284). Using samples at recruitment, serum protein profiles using the Olink Proximity Extension Assay platform was assessed for association with future development of CD and with other baseline biomarkers as follows: serum antimicrobial antibodies (AS: positive antibody sum) (Prometheus); faecal calprotectin (FCP); gut barrier function using the fractional excretion of lactulose-to-mannitol ratio (LMR) assay.RESULTS: We identified 25 of 446 serum proteins significantly associated with future development of CD. C-X-C motif chemokine 9 (CXCL9) had the highest OR with future risk of CD (OR=2.07 per SD, 95% CI 1.58 to 2.73, q=7.9e-5), whereas matrix extracellular phosphoglycoprotein had the lowest OR (OR 0.44, 95% CI 0.29 to 0.66, q=0.02). Notably, CXCL9 was the only analyte significantly associated with all other CD-risk biomarkers with consistent direction of effect (FCP: OR=2.21; LMR: OR=1.67; AS: OR=1.59) (q<0.05 for all).CONCLUSION: We identified serum proteomic signatures associated with future CD development, reflecting potential early biological processes of immune and barrier dysfunction.
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