SwePub
Sök i SwePub databas

  Utökad sökning

Träfflista för sökning "WFRF:(Marschall Hanns Ulrich) ;pers:(Marschall Hanns Ulrich)"

Sökning: WFRF:(Marschall Hanns Ulrich) > Marschall Hanns Ulrich

  • Resultat 1-10 av 155
Sortera/gruppera träfflistan
   
NumreringReferensOmslagsbildHitta
1.
  • Fickert, Peter, et al. (författare)
  • Characterization of animal models for primary sclerosing cholangitis (PSC).
  • 2014
  • Ingår i: Journal of hepatology. - : Elsevier BV. - 1600-0641 .- 0168-8278. ; 60:6
  • Forskningsöversikt (refereegranskat)abstract
    • Primary sclerosing cholangitis (PSC) is a chronic cholangiopathy characterized by biliary fibrosis, development of cholestasis and end stage liver disease, high risk of malignancy, and frequent need for liver transplantation. The poor understanding of its pathogenesis is also reflected in the lack of effective medical treatment. Well-characterized animal models are utterly needed to develop novel pathogenetic concepts and study new treatment strategies. Currently there is no consensus on how to evaluate and characterize potential PSC models, which makes direct comparison of experimental results and effective exchange of study material between research groups difficult. The International Primary Sclerosing Cholangitis Study Group (IPSCSG) has therefore summarized these key issues in a position paper proposing standard requirements for the study of animal models of PSC.
  •  
2.
  • Marschall, Hanns-Ulrich, et al. (författare)
  • When bile acids don't get amidated.
  • 2013
  • Ingår i: Gastroenterology. - : Elsevier BV. - 1528-0012 .- 0016-5085. ; 144:5, s. 870-3
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
  •  
3.
  • Nevens, Frederik, et al. (författare)
  • A Placebo-Controlled Trial of Obeticholic Acid in Primary Biliary Cholangitis.
  • 2016
  • Ingår i: The New England journal of medicine. - 1533-4406. ; 375:7, s. 631-43
  • Tidskriftsartikel (refereegranskat)abstract
    • Primary biliary cholangitis (formerly called primary biliary cirrhosis) can progress to cirrhosis and death despite ursodiol therapy. Alkaline phosphatase and bilirubin levels correlate with the risk of liver transplantation or death. Obeticholic acid, a farnesoid X receptor agonist, has shown potential benefit in patients with this disease.
  •  
4.
  • Nuñez Durán, Esther, et al. (författare)
  • Serine/threonine protein kinase 25 antisense oligonucleotide treatment reverses glucose intolerance, insulin resistance, and nonalcoholic fatty liver disease in mice.
  • 2018
  • Ingår i: Hepatology communications. - : Ovid Technologies (Wolters Kluwer Health). - 2471-254X. ; 2:1, s. 69-83
  • Tidskriftsartikel (refereegranskat)abstract
    • Nonalcoholic fatty liver disease (NAFLD) contributes to the pathogenesis of type 2 diabetes and cardiovascular disease, and patients with nonalcoholic steatohepatitis (NASH) are also at risk of developing cirrhosis, liver failure, and hepatocellular carcinoma. To date, no specific therapy exists for NAFLD/NASH, which has been recognized as one of the major unmet medical needs of the twenty-first century. We recently identified serine/threonine protein kinase (STK)25 as a critical regulator of energy homeostasis and NAFLD progression. Here, we investigated the effect of antisense oligonucleotides (ASOs) targeting Stk25 on the metabolic and molecular phenotype of mice after chronic exposure to dietary lipids. We found that Stk25 ASOs efficiently reversed high-fat diet-induced systemic hyperglycemia and hyperinsulinemia, improved whole-body glucose tolerance and insulin sensitivity, and ameliorated liver steatosis, inflammatory infiltration, apoptosis, hepatic stellate cell activation, and nutritional fibrosis in obese mice. Moreover, Stk25 ASOs suppressed the abundance of liver acetyl-coenzyme A carboxylase (ACC) protein, a key regulator of both lipid oxidation and synthesis, revealing the likely mechanism underlying repression of hepatic fat accumulation by ASO treatment. We also found that STK25 protein levels correlate significantly and positively with NASH development in human liver biopsies, and several common nonlinked single-nucleotide polymorphisms in the human STK25 gene are associated with altered liver fat, supporting a critical role of STK25 in the pathogenesis of NAFLD in humans. Conclusion: Preclinical validation for the metabolic benefit of pharmacologically inhibiting STK25 in the context of obesity is provided. Therapeutic intervention aimed at reducing STK25 function may provide a new strategy for the treatment of patients with NAFLD, type 2 diabetes, and related complex metabolic diseases. (Hepatology Communications 2018;2:69-83).
  •  
5.
  • Abdel-Khalik, Jonas, et al. (författare)
  • Bile acid biosynthesis in Smith-Lemli-Opitz syndrome bypassing cholesterol: Potential importance of pathway intermediates.
  • 2021
  • Ingår i: The Journal of steroid biochemistry and molecular biology. - : Elsevier BV. - 1879-1220 .- 0960-0760. ; 206
  • Tidskriftsartikel (refereegranskat)abstract
    • Bile acids are the end products of cholesterol metabolism secreted into bile. They are essential for the absorption of lipids and lipid soluble compounds from the intestine. Here we have identified a series of unusual Δ5-unsaturated bile acids in plasma and urine of patients with Smith-Lemli-Opitz syndrome (SLOS), a defect in cholesterol biosynthesis resulting in elevated levels of 7-dehydrocholesterol (7-DHC), an immediate precursor of cholesterol. Using liquid chromatography - mass spectrometry (LC-MS) we have uncovered a pathway of bile acid biosynthesis in SLOS avoiding cholesterol starting with 7-DHC and proceeding through 7-oxo and 7β-hydroxy intermediates. This pathway also occurs to a minor extent in healthy humans, but elevated levels of pathway intermediates could be responsible for some of the features SLOS. The pathway is also active in SLOS affected pregnancies as revealed by analysis of amniotic fluid. Importantly, intermediates in the pathway, 25-hydroxy-7-oxocholesterol, (25R)26-hydroxy-7-oxocholesterol, 3β-hydroxy-7-oxocholest-5-en-(25R)26-oic acid and the analogous 7β-hydroxysterols are modulators of the activity of Smoothened (Smo), an oncoprotein that mediates Hedgehog (Hh) signalling across membranes during embryogenesis and in the regeneration of postembryonic tissue. Computational docking of the 7-oxo and 7β-hydroxy compounds to the extracellular cysteine rich domain of Smo reveals that they bind in the same groove as both 20S-hydroxycholesterol and cholesterol, known activators of the Hh pathway.
  •  
6.
  • Abu-Hayyeh, Shadi, et al. (författare)
  • Intrahepatic cholestasis of pregnancy levels of sulfated progesterone metabolites inhibit farnesoid X receptor resulting in a cholestatic phenotype.
  • 2013
  • Ingår i: Hepatology. - : Ovid Technologies (Wolters Kluwer Health). - 0270-9139 .- 1527-3350. ; 57:2
  • Tidskriftsartikel (refereegranskat)abstract
    • Intrahepatic cholestasis of pregnancy (ICP) is the most prevalent pregnancy-specific liver disease and is associated with an increased risk of adverse fetal outcomes, including preterm labor and intrauterine death. The endocrine signals that cause cholestasis are not known but 3α-sulfated progesterone metabolites have been shown to be elevated in ICP, leading us to study the impact of sulfated progesterone metabolites on farnesoid X receptor (FXR)-mediated bile acid homeostasis pathways. Here we report that the 3β-sulfated progesterone metabolite epiallopregnanolone sulfate is supraphysiologically raised in the serum of ICP patients. Mice challenged with cholic acid developed hypercholanemia and a hepatic gene expression profile indicative of FXR activation. However, coadministration of epiallopregnanolone sulfate with cholic acid exacerbated the hypercholanemia and resulted in aberrant gene expression profiles for hepatic bile acid-responsive genes consistent with cholestasis. We demonstrate that levels of epiallopregnanolone sulfate found in ICP can function as a partial agonist for FXR, resulting in the aberrant expression of bile acid homeostasis genes in hepatoma cell lines and primary human hepatocytes. Furthermore, epiallopregnanolone sulfate inhibition of FXR results in reduced FXR-mediated bile acid efflux and secreted FGF19. Using cofactor recruitment assays, we show that epiallopregnanolone sulfate competitively inhibits bile acid-mediated recruitment of cofactor motifs to the FXR-ligand binding domain. Conclusion: Our results reveal a novel molecular interaction between ICP-associated levels of the 3β-sulfated progesterone metabolite epiallopregnanolone sulfate and FXR that couples the endocrine component of pregnancy in ICP to abnormal bile acid homeostasis. (HEPATOLOGY 2012;).
  •  
7.
  • Abu-Hayyeh, S., et al. (författare)
  • Prognostic and Mechanistic Potential of Progesterone Sulfates in Intrahepatic Cholestasis of Pregnancy and Pruritus Gravidarum
  • 2016
  • Ingår i: Hepatology. - : Ovid Technologies (Wolters Kluwer Health). - 0270-9139 .- 1527-3350. ; 63:4, s. 1287-1298
  • Tidskriftsartikel (refereegranskat)abstract
    • 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.
  •  
8.
  • Al-Dury, Samer, et al. (författare)
  • Ileal Bile Acid Transporter Inhibition for the Treatment of Chronic Constipation, Cholestatic Pruritus, and NASH
  • 2018
  • Ingår i: Frontiers in Pharmacology. - : Frontiers Media SA. - 1663-9812. ; 9
  • Tidskriftsartikel (refereegranskat)abstract
    • Bile acids are synthesized from cholesterol in the liver, excreted with bile into the duodenum, almost completely taken up again in the distal ileum and finally returned to the liver with portal blood in a process termed enterohepatic circulation. Bile acid synthesis, excretion, and reuptake are tightly regulated. The apical sodium-dependent bile acid transporter [ASBT; also known as ileal bile acid transporter (IBAT) and SLC10A2] is pivotal for the almost complete reabsorption of conjugated bile acids in the ileum. Dysfunctional IBAT may be the cause of bile acid diarrhea. Pharmacological IBAT inhibition results in an increased bile acid load in the colon and subsequently a lower bile acid pool, which is associated with improved liver histology in animal models of cholestatic liver disease and non-alcoholic steatohepatitis (NASH). In humans, IBAT inhibitors have been tested in clinical trials with widely different indications: in patients with idiopathic chronic constipation, an increased number of bowel movements was observed. In adult and pediatric cholestatic liver diseases with pruritus, various IBAT inhibitors showed potential to improve itching. Adverse events of IBAT inhibitors, based on their mode of action, are abdominal pain and diarrhea which might patients to withdraw from study medications. So far, no data are available of a study of IBAT inhibitors in patients with NASH. In this review we summarize the preclinical and most recent clinical studies with various IBAT inhibitors and discuss the difficulties that should be addressed in future studies.
  •  
9.
  • Al-Dury, Samer, et al. (författare)
  • Obeticholic acid may increase the risk of gallstone formation in susceptible patients.
  • 2019
  • Ingår i: Journal of hepatology. - : Elsevier BV. - 1600-0641 .- 0168-8278. ; 71:5, s. 986-991
  • Tidskriftsartikel (refereegranskat)abstract
    • The nuclear farnesoid X receptor (FXR) agonist obeticholic acid (OCA) has been developed for the treatment of liver diseases. We aimed to determine whether OCA treatment increases the risk of gallstone formation.Twenty patients awaiting laparoscopic cholecystectomy were randomized to treatment with OCA (25 mg/day) or placebo for three weeks before surgery. Serum bile acids (BAs), the BA synthesis marker C4 (7α-hydroxy-cholest-4-ene-3-one), and fibroblast growth factor 19 (FGF19) were measured before and after treatment. During surgery, biopsies from the liver and the whole bile-filled gallbladder were collected for analyses of gene expression, biliary lipids and FGF19.In serum, OCA increased FGF19 (from 95.0±8.5 to 234.4±35.6 ng/L) and decreased C4 (from 31.4±22.8 to 2.8±4.0 nmol/L) and endogenous BAs (from 1312.2±236.2 to 517.7±178.9 nmol/L; all p<0.05). At surgery, BAs in gallbladder bile were lower in OCA patients than controls (OCA, 77.9±53.6 mmol/L; placebo, 196.4±99.3 mmol/L; p<0.01), resulting in a higher cholesterol saturation index (OCA, 2.8±1.1; placebo, 1.8±0.8; p < 0.05). In addition, hydrophobic OCA conjugates accounted for 13.6±5.0% of gallbladder BAs after OCA treatment, resulting in a higher hydrophobicity index (OCA, 0.43±0.09; placebo, 0.34±0.07, p<0.05). Gallbladder FGF19 was three-fold higher in OCA patients than in controls (OCA, 40.3±16.5 ng/L; placebo, 13.5±13.1 ng/mL; p<0.005). Gene expression analysis indicated a mainly gallbladder epithelial origin of FGF19.Our results show for the first time an enrichment of FGF19 in human bile after OCA treatment. In accordance with its murine homolog FGF15, FGF19 might trigger relaxation and filling of the gallbladder which, in combination with increased cholesterol saturation and BA hydrophobicity, would enhance the risk for gallstone development.Obeticholic acid increased human gallbladder cholesterol saturation and bile acid hydrophobicity, both decreasing cholesterol solubility in bile. Together with increased hepatobiliary FGF19, our findings suggest that pharmacological FXR activation increases the risk of gallstone formation.
  •  
10.
  • Al-Dury, Samer, et al. (författare)
  • Pilot study with IBAT inhibitor A4250 for the treatment of cholestatic pruritus in primary biliary cholangitis
  • 2018
  • Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 8
  • Tidskriftsartikel (refereegranskat)abstract
    • Pruritus is a common complication of cholestatic liver diseases. Inhibition of the ileal bile acid transporter (IBAT/ASBT) may emerge as treatment option. Our aim was to assess tolerability and effect on pruritus of the selective IBAT inhibitor A4250 in patients with primary biliary cholangitis (PBC). Ten patients with PBC and bile acid sequestrant treatment of cholestatic pruritus were after a two-week wash out of the bile acid sequestrant treated with either 0.75 mg (n = 4) or 1.5 mg (n = 5) of A4250 for four weeks. Patients' pruritus was assessed by Visual Analogue Scale (VAS), 5-D itch scale and the pruritus module of the PBC40 questionnaire. Plasma bile acids and 7 alpha-hydroxy-4-cholesten-3-one were measured by UPLC-MS/MS, plasma fibroblast growth factor 19 by ELISA, and serum autotaxin activity by homemade assay. All nine patients exposed to A4250 reported a remarkable improvement in pruritus, until none or mild according to 5-D itch, VAS and PBC40 pruritus. Five patients finished the study prematurely due to abdominal pain (5/5) and diarrhoea (4/5). The high incidence of probably bile acid malabsorption-related diarrhoea and abdominal pain in the bile acid sequestrant pre-treated population indicates that the start dose of A4250 may have been too high for adult patients.
  •  
Skapa referenser, mejla, bekava och länka
  • Resultat 1-10 av 155
Typ av publikation
tidskriftsartikel (153)
annan publikation (1)
forskningsöversikt (1)
Typ av innehåll
refereegranskat (146)
övrigt vetenskapligt/konstnärligt (9)
Författare/redaktör
Ståhlman, Marcus, 19 ... (23)
Wahlström, Annika, 1 ... (22)
Mahlapuu, Margit, 19 ... (16)
Cansby, Emmelie, 198 ... (15)
Williamson, C (13)
visa fler...
Borén, Jan, 1963 (12)
Bäckhed, Fredrik, 19 ... (11)
Trauner, Michael (11)
Williamson, Catherin ... (9)
Chambers, J. (9)
Trauner, M (9)
Bergquist, A (8)
Nilsson, Emma (7)
Bergquist, Annika (7)
Ovadia, C. (7)
Molinaro, Antonio (7)
Werner, Mårten (7)
Kechagias, Stergios (6)
Lovgren-Sandblom, A. (6)
Xia, Ying (6)
Fändriks, Lars, 1956 (6)
Wahlin, S. (6)
Nuñez Durán, Esther (6)
Beuers, U. (5)
Rorsman, Fredrik (5)
Al-Dury, Samer (5)
Fickert, Peter (5)
Wagner, Martin (5)
Pares, A (5)
Schramm, C (5)
Nyhlin, Nils, 1971- (5)
Ekstedt, Mattias (4)
Dixon, P. H. (4)
Seed, P. T. (4)
Franke, A (4)
Wallenius, Ville, 19 ... (4)
Ludvigsson, Jonas F. ... (4)
Rorsman, Fredrik, Do ... (4)
Hagström, Hannes (4)
Thorell, Anders (4)
Ellinghaus, D (4)
Holm, K (4)
Milkiewicz, P (4)
Schrumpf, E (4)
Amrutkar, Manoj (4)
Bluher, M. (4)
Henricsson, Marcus, ... (4)
Casselbrant, Anna, 1 ... (4)
Bergh, Per-Olof (4)
visa färre...
Lärosäte
Göteborgs universitet (144)
Karolinska Institutet (39)
Örebro universitet (12)
Uppsala universitet (6)
Umeå universitet (5)
Lunds universitet (5)
visa fler...
Chalmers tekniska högskola (5)
Linköpings universitet (1)
visa färre...
Språk
Engelska (154)
Svenska (1)
Forskningsämne (UKÄ/SCB)
Medicin och hälsovetenskap (144)
Naturvetenskap (17)
Lantbruksvetenskap (1)

År

Kungliga biblioteket hanterar dina personuppgifter i enlighet med EU:s dataskyddsförordning (2018), GDPR. Läs mer om hur det funkar här.
Så här hanterar KB dina uppgifter vid användning av denna tjänst.

 
pil uppåt Stäng

Kopiera och spara länken för att återkomma till aktuell vy