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Neurosteroid activa...
Neurosteroid activation of gaba-a receptors : a potential treatment target for symptoms in primary biliary cholangitis?
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- Wetten, Aaron (författare)
- Translational and Clinical Research Institute, Newcastle University, Newcastle-upon-Tyne, United Kingdom; Freeman Hospital, Newcastle-upon-Tyne, United Kingdom
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- Ogle, Laura (författare)
- Translational and Clinical Research Institute, Newcastle University, Newcastle-upon-Tyne, United Kingdom; Freeman Hospital, Newcastle-upon-Tyne, United Kingdom
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- Mells, George (författare)
- Department of Human Genetics, University of Cambridge, Cambridge, United Kingdom
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- Hegade, Vinod S. (författare)
- Leeds Liver Unit, St James' University Hospital, Leeds, United Kingdom
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- Jopson, Laura (författare)
- Translational and Clinical Research Institute, Newcastle University, Newcastle-upon-Tyne, United Kingdom; Freeman Hospital, Newcastle-upon-Tyne, United Kingdom
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- Corrigan, Margaret (författare)
- Liverpool University Hospitals NHS Foundation Trust, Liverpool, United Kingdom
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- Palmer, Jeremy (författare)
- Translational and Clinical Research Institute, Newcastle University, Newcastle-upon-Tyne, United Kingdom
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- Johansson, Maja (författare)
- Umecrine Cognition AB, Solna, Sweden
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- Bäckström, Torbjörn (författare)
- Umeå universitet,Obstetrik och gynekologi,Umecrine Cognition AB, Solna, Sweden
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- Doverskog, Magnus (författare)
- Umecrine Cognition AB, Solna, Sweden
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- Jones, David E. J. (författare)
- Translational and Clinical Research Institute, Newcastle University, Newcastle-upon-Tyne, United Kingdom; Freeman Hospital, Newcastle-upon-Tyne, United Kingdom
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- Dyson, Jessica K. (författare)
- Translational and Clinical Research Institute, Newcastle University, Newcastle-upon-Tyne, United Kingdom; Freeman Hospital, Newcastle-upon-Tyne, United Kingdom
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(creator_code:org_t)
- Hindawi Publishing Corporation, 2022
- 2022
- Engelska.
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Ingår i: Canadian journal of gastroenterology & hepatology. - : Hindawi Publishing Corporation. - 2291-2789 .- 2291-2797. ; 2022
- Relaterad länk:
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https://doi.org/10.1...
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https://umu.diva-por... (primary) (Raw object)
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
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- Background and Aims: A third of patients with primary biliary cholangitis (PBC) experience poorly understood cognitive symptoms, with a significant impact on quality of life (QOL), and no effective medical treatment. Allopregnanolone, a neurosteroid, is a positive allosteric modulator of gamma-aminobutyricacid-A (GABA-A) receptors, associated with disordered mood, cognition, and memory. This study explored associations between allopregnanolone and a disease-specific QOL scoring system (PBC-40) in PBC patients.Method: Serum allopregnanolone levels were measured in 120 phenotyped PBC patients and 40 age and gender-matched healthy controls. PBC subjects completed the PBC-40 at recruitment. Serum allopregnanolone levels were compared across PBC-40 domains for those with none/mild symptoms versus severe symptoms.Results: There were no overall differences in allopregnanolone levels between healthy controls (median = 0.03 ng/ml (IQR = 0.025)) and PBC patients (0.031 (0.42), p = 0.42). Within the PBC cohort, higher allopregnanolone levels were observed in younger patients (r (120) = -0.53, p < 0.001) but not healthy controls (r (39) = -0.21, p = 0.21). Allopregnanolone levels were elevated in the PBC-40 domains, cognition (u = 1034, p = 0.02), emotional (u = 1374, p = 0.004), and itch (u = 795, p = 0.03). Severe cognitive symptoms associated with a younger age: severe (50 (12)) vs. none (60 (13); u = 423 p = 0.001).Conclusion: Elevated serum allopregnanolone is associated with severe cognitive, emotional, and itch symptoms in PBC, in keeping with its known action on GABA-A receptors. Existing novel compounds targeting allopregnanolone could offer new therapies in severely symptomatic PBC, satisfying a significant unmet need.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Gastroenterologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Gastroenterology and Hepatology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Hälsovetenskap -- Folkhälsovetenskap, global hälsa, socialmedicin och epidemiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Health Sciences -- Public Health, Global Health, Social Medicine and Epidemiology (hsv//eng)
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Till lärosätets databas
- Av författaren/redakt...
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Wetten, Aaron
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Ogle, Laura
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Mells, George
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Hegade, Vinod S.
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Jopson, Laura
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Corrigan, Margar ...
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visa fler...
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Palmer, Jeremy
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Johansson, Maja
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Bäckström, Torbj ...
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Doverskog, Magnu ...
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Jones, David E. ...
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Dyson, Jessica K ...
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visa färre...
- Om ämnet
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- MEDICIN OCH HÄLSOVETENSKAP
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MEDICIN OCH HÄLS ...
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och Klinisk medicin
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och Gastroenterologi
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- MEDICIN OCH HÄLSOVETENSKAP
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MEDICIN OCH HÄLS ...
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och Hälsovetenskap
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och Folkhälsovetensk ...
- Artiklar i publikationen
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Canadian journal ...
- Av lärosätet
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Umeå universitet