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https://www.readbyqxmd.com/read/26641452/pathogenesis-and-management-of-pruritus-in-pbc-and-psc
#1
Andreas E Kremer, Barbara Namer, Ruth Bolier, Michael J Fischer, Ronald P Oude Elferink, Ulrich Beuers
Pruritus is a preeminent symptom in patients with chronic cholestatic liver disorders such as primary biliary cirrhosis and primary sclerosing cholangitis. More than two-thirds of these patients experience itching during the course of their disease. This symptom is also frequently observed in patients with other causes of cholestasis such as cholangiocarcinoma, inherited forms of cholestasis and intrahepatic cholestasis of pregnancy, but may accompany almost any other liver disease. The pathogenesis of pruritus of cholestasis remains largely elusive...
2015: Digestive Diseases
https://www.readbyqxmd.com/read/25297933/variant-adiponutrin-confers-genetic-protection-against-cholestatic-itch
#2
Marcin Krawczyk, Malgorzata Milkiewicz, Hanns-Ulrich Marschall, Clemens Bartz, Frank Grünhage, Ewa Wunsch, Piotr Milkiewicz, Frank Lammert
Lysophosphatidic acid (LPA) mediates cholestatic pruritus. Recently the enzyme PNPLA3, expressed in liver and skin, was demonstrated to metabolise LPA. Here we assess the association of the PNPLA3 variant p.Ile148Met, known to be associated with (non-)alcoholic fatty liver disease (NAFLD) in genome-wide association studies, with cholestatic itch in 187 patients with primary biliary cirrhosis (PBC) and 250 PBC-free controls as well as 201 women with intrahepatic cholestasis of pregnancy (ICP) and 198 female controls without a history of ICP...
October 9, 2014: Scientific Reports
https://www.readbyqxmd.com/read/25218302/lysophosphatidic-acid-and-signaling-in-sensory-neurons
#3
REVIEW
Ronald P J Oude Elferink, Ruth Bolier, Ulrich H Beuers
Lysophosphatidic acid is a potent signaling lipid molecule that has initially been characterized as a growth factor. However, later studies have revealed many more functions such as modulation of cell shape, cell migration, prevention of apoptosis, platelet aggregation, wound healing, osteoclast differentiation, vasopressor activity, embryo implantation, angiogenesis, lung fibrosis, hair growth and more. The molecule mainly acts through the activation of a set of at least 6 G-protein-coupled receptors (LPA1-6), but intracellular LPA was also shown to signal through the activation of the nuclear receptor PPARγ...
January 2015: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/24807046/pruritus-in-cholestasis-facts-and-fiction
#4
REVIEW
Ulrich Beuers, Andreas E Kremer, Ruth Bolier, Ronald P J Oude Elferink
Pruritus is a common symptom in patients with cholestatic liver diseases such as primary biliary cirrhosis, primary sclerosing cholangitis, intrahepatic cholestasis of pregnancy, or hereditary pediatric cholestatic disorders and may accompany, although less frequently, many other liver diseases. Recent findings indicate that lysophosphatidic acid (LPA), a potent neuronal activator, and autotaxin (ATX; ectonucleotide pyrophosphatase/phosphodiesterase 2), the enzyme which forms LPA, may form a key element of the long-sought pruritogenic signaling cascade in cholestatic patients suffering from itch...
July 2014: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/24641902/potentials-of-the-circulating-pruritogenic-mediator-lysophosphatidic-acid-in-development-of-allergic-skin-inflammation-in-mice-role-of-blood-cell-associated-lysophospholipase-d-activity-of-autotaxin
#5
Yoshibumi Shimizu, Yoshiyuki Morikawa, Shinichi Okudaira, Shigenobu Kimoto, Tamotsu Tanaka, Junken Aoki, Akira Tokumura
Itching and infiltration of immune cells are important hallmarks of atopic dermatitis (AD). Although various studies have focused on peripheral mediator-mediated mechanisms, systemic mediator-mediated mechanisms are also important in the pathogenesis and development of AD. Herein, we found that intradermal injection of lysophosphatidic acid (LPA), a bioactive phospholipid, induces scratching responses by Institute of Cancer Research mice through LPA1 receptor- and opioid μ receptor-mediating mechanisms, indicating its potential as a pruritogen...
May 2014: American Journal of Pathology
https://www.readbyqxmd.com/read/22473838/serum-autotaxin-is-increased-in-pruritus-of-cholestasis-but-not-of-other-origin-and-responds-to-therapeutic-interventions
#6
COMPARATIVE STUDY
Andreas E Kremer, Remco van Dijk, Pamela Leckie, Frank G Schaap, Edith M M Kuiper, Thomas Mettang, Katrin S Reiners, Ulrike Raap, Henk R van Buuren, Karel J van Erpecum, Nathan A Davies, Christian Rust, Andreas Engert, Rajiv Jalan, Ronald P J Oude Elferink, Ulrich Beuers
UNLABELLED: Pruritus is a seriously disabling symptom accompanying many cholestatic liver disorders. Recent experimental evidence implicated the lysophospholipase, autotaxin (ATX), and its product, lysophosphatidic acid (LPA), as potential mediators of cholestatic pruritus. In this study, we highlight that increased serum ATX levels are specific for pruritus of cholestasis, but not pruritus of uremia, Hodgkin's disease, or atopic dermatitis. Treatment of patients with cholestasis with the bile salt sequestrant, colesevelam, but not placebo, effectively reduced total serum bile salts and fibroblast growth factor 19 levels, but only marginally altered pruritus intensity and ATX activity...
October 2012: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/21809485/pathophysiology-and-current-management-of-pruritus-in-liver-disease
#7
REVIEW
Andreas E Kremer, Ronald P J Oude Elferink, Ulrich Beuers
Pruritus is frequently reported by patients with cholestatic hepatobiliary diseases such as primary biliary cirrhosis, primary sclerosing cholangitis, intrahepatic cholestasis of pregnancy and hereditary cholestatic syndromes, but may accompany almost any other liver disease. Increased concentrations of bile salts, histamine, progesterone metabolites or endogenous opioids have been controversially discussed as potential pruritogens in cholestasis in the past. Most recently, novel insights unravelled lysophosphatidic acid (LPA), a potent neuronal activator, as a potential pruritogen in pruritus of cholestasis...
February 2011: Clinics and Research in Hepatology and Gastroenterology
https://www.readbyqxmd.com/read/21691108/the-molecular-mechanism-of-cholestatic-pruritus
#8
Ronald P J Oude Elferink, Andreas E Kremer, Job J W W Martens, Ulrich H Beuers
Pruritus is a frequent symptom in patients with cholestatic liver diseases. Pruritus can be excruciating and, in rare cases, become a primary indication for liver transplantation. The molecular mechanism of itch signal transduction is largely unclear. It was our hypothesis that compounds which accumulate in the circulation during cholestasis act as direct or indirect pruritogens by affecting signaling in itch fibers. To test this, we screened plasma samples of a large group of patients with various cholestatic conditions for their capacity to activate neuroblastoma cells...
2011: Digestive Diseases
https://www.readbyqxmd.com/read/21451412/mediators-of-pruritus-during-cholestasis
#9
REVIEW
Ronald P J Oude Elferink, Andreas E Kremer, Ulrich Beuers
PURPOSE OF REVIEW: Pruritus is a frequent symptom in patients with cholestatic liver diseases. Itching may be excruciating, may seriously impair quality of life and even induce suicidal ideation in the most severe cases. RECENT FINDINGS: The molecular mechanism of itch signal transduction in cholestasis is largely unclear. It may be caused or potentiated by compounds that accumulate in the circulation during cholestasis, which either directly or indirectly affect signalling in itch fibres...
May 2011: Current Opinion in Gastroenterology
https://www.readbyqxmd.com/read/20546739/lysophosphatidic-acid-is-a-potential-mediator-of-cholestatic-pruritus
#10
Andreas E Kremer, Job J W W Martens, Wim Kulik, Franziska Ruëff, Edith M M Kuiper, Henk R van Buuren, Karel J van Erpecum, Jurate Kondrackiene, Jesus Prieto, Christian Rust, Victoria L Geenes, Catherine Williamson, Wouter H Moolenaar, Ulrich Beuers, Ronald P J Oude Elferink
BACKGROUND & AIMS: Pruritus is a common and disabling symptom in cholestatic disorders. However, its causes remain unknown. We hypothesized that potential pruritogens accumulate in the circulation of cholestatic patients and activate sensory neurons. METHODS: Cytosolic free calcium ([Ca(2+)](i)) was measured in neuronal cell lines by ratiometric fluorometry upon exposure to serum samples from pruritic patients with intrahepatic cholestasis of pregnancy (ICP), primary biliary cirrhosis (PBC), other cholestatic disorders, and pregnant, healthy, and nonpruritic disease controls...
September 2010: Gastroenterology
https://www.readbyqxmd.com/read/15292655/itch-scratch-responses-induced-by-lysophosphatidic-acid-in-mice
#11
Terumasa Hashimoto, Hisayuki Ohata, Kazutaka Momose
The present investigation was conducted in order to determine whether lysophosphatidic acid (LPA) induces itch-scratch responses (ISRs) in mice. Intradermal administration of LPA induces ISRs; furthermore, the time course for LPA-induced ISRs was similar to that for histamine-induced responses. Comparative study of the pruritogenic activity revealed that histamine possessed a potent effect characterized by a dose-response relationship; however, prostaglandin D2 failed to induce this response. Pretreatment with ketotifen, a histamine H1 receptor antagonist, and capsaicin inhibited LPA-induced ISRs...
September 2004: Pharmacology
https://www.readbyqxmd.com/read/6987109/primary-cutaneous-amyloidosis-clinical-laboratorial-and-histopathological-study-of-25-cases-identification-of-gammaglobulins-and-c3-in-the-lesions-by-immunofluorescence
#12
M C Habermann, M R Montenegro
25 cases of primary cutaneous amyloidosis are studied. 16 patients had macular amyloidosis (MPA) and 9 lichen amyloidosus (LPA). gamma-Globulins were increased in 50% of the patients. IgG and IgA were increased in the serum of 5 and 3 patients with MPA and 4 and 2 patients with LPA, respectively. Volume of amyloid deposits was similar in both forms. By direct immunofluorescence we demonstrated IgG in the amyloid deposits of 21 of the 25 cases and C3 in 13; IgM was present in 9 cases of MPA and in 3 cases of LPA...
1980: Dermatologica
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