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Prognostic and Mech...
Prognostic and Mechanistic Potential of Progesterone Sulfates in Intrahepatic Cholestasis of Pregnancy and Pruritus Gravidarum
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Abu-Hayyeh, S. (författare)
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Ovadia, C. (författare)
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Lieu, T. (författare)
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Jensen, D. D. (författare)
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Chambers, J. (författare)
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Dixon, P. H. (författare)
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- Lovgren-Sandblom, A. (författare)
- Karolinska Institutet
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Bolier, R. (författare)
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Tolenaars, D. (författare)
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Kremer, A. E. (författare)
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Syngelaki, A. (författare)
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Noori, M. (författare)
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Williams, D. (författare)
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Marin, J. J. G. (författare)
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Monte, M. J. (författare)
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Nicolaides, K. H. (författare)
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Beuers, U. (författare)
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Oude-Elferink, R. (författare)
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Seed, P. T. (författare)
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Chappell, L. (författare)
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- Marschall, Hanns-Ulrich, 1954 (författare)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Institute of Medicine, Department of Molecular and Clinical Medicine
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Bunnett, N. W. (författare)
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Williamson, C. (författare)
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(creator_code:org_t)
- 2015-12-28
- 2016
- Engelska.
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Ingår i: Hepatology. - : Ovid Technologies (Wolters Kluwer Health). - 0270-9139 .- 1527-3350. ; 63:4, s. 1287-1298
- Relaterad länk:
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https://aasldpubs.on...
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https://gup.ub.gu.se...
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https://doi.org/10.1...
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http://kipublication...
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Abstract
Ämnesord
Stäng
- A challenge in obstetrics is to distinguish pathological symptoms from those associated with normal changes of pregnancy, typified by the need to differentiate whether gestational pruritus of the skin is an early symptom of intrahepatic cholestasis of pregnancy (ICP) or due to benign pruritus gravidarum. ICP is characterized by raised serum bile acids and complicated by spontaneous preterm labor and stillbirth. A biomarker for ICP would be invaluable for early diagnosis and treatment and to enable its differentiation from other maternal diseases. Three progesterone sulfate compounds, whose concentrations have not previously been studied, were newly synthesized and assayed in the serum of three groups of ICP patients and found to be significantly higher in ICP at 9-15 weeks of gestation and prior to symptom onset (group 1 cases/samples: ICP n = 35/80, uncomplicated pregnancy = 29/100), demonstrating that all three progesterone sulfates are prognostic for ICP. Concentrations of progesterone sulfates were associated with itch severity and, in combination with autotaxin, distinguished pregnant women with itch that would subsequently develop ICP from pruritus gravidarum (group 2: ICP n = 41, pruritus gravidarum n = 14). In a third group of first-trimester samples all progesterone sulfates were significantly elevated in serum from low-risk asymptomatic women who subsequently developed ICP (ICP/uncomplicated pregnancy n = 54/51). Finally, we show mechanistically that progesterone sulfates mediate itch by evoking a Tgr5-dependent scratch response in mice. Conclusion: Our discovery that sulfated progesterone metabolites are a prognostic indicator for ICP will help predict onset of ICP and distinguish it from benign pruritus gravidarum, enabling targeted obstetric care to a high-risk population. Delineation of a progesterone sulfate-TGR5 pruritus axis identifies a therapeutic target for itch management in ICP.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Infektionsmedicin (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Infectious Medicine (hsv//eng)
Nyckelord
- bile-acid levels
- metabolites
- tgr5
- expression
- urine
- women
- serum
- term
- Gastroenterology & Hepatology
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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Till lärosätets databas
- Av författaren/redakt...
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Abu-Hayyeh, S.
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Ovadia, C.
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Lieu, T.
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Jensen, D. D.
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Chambers, J.
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Dixon, P. H.
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visa fler...
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Lovgren-Sandblom ...
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Bolier, R.
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Tolenaars, D.
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Kremer, A. E.
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Syngelaki, A.
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Noori, M.
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Williams, D.
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Marin, J. J. G.
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Monte, M. J.
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Nicolaides, K. H ...
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Beuers, U.
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Oude-Elferink, R ...
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Seed, P. T.
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Chappell, L.
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Marschall, Hanns ...
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Bunnett, N. W.
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Williamson, C.
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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 Infektionsmedici ...
- Artiklar i publikationen
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Hepatology
- Av lärosätet
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Göteborgs universitet
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Karolinska Institutet