Is osteopenia a peculiar association with primary biliary cirrhosis (PBC)?
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49 URSODEOXYCHOLATE AND TAUROURSODBOXYCHOLATE INHIBITION OF CHOLANGIOCYTP PROLIFERATIVE AND SECRETIVE FUNCTIONS IS ASSOCIATED WITH ACTIVATION OF CaZ+-DEPENDENT PKC ALPHA L. Baiocchi*, M. Angelica*, S. Glaser~, G. L&ages & G. Alpinig. ‘Cattedra di Gastmentmologia, Universitd di Rmna’Tor Ver@ Rome, ITALY: $Dept. Of lntemal Medicine and Physiology, Texas A&M University (Temple, TX-USA). Universita’Tor Vergata Background : Hydrophilic bile acids (BA) such as Urscdeoxycholic (UDCA) and Taumtnsodmxycholic (TUDCA) acid a-ecommonly used in the therapy ofhuman cholestaticliver diseases,however their effect on proliferative andsmretive cholangiocytes activities, in cholestatic conditions was never extensively assessed.Aims: i) to determineif UDCA or TUDCA chronic feeding modulatesthe increasedcholangiocytegmwib and secretionin bile duct ligated (BDL) rats; ii) to evaluateif thesepostulatedeffects require aBA uptakemechanismand if are dependenton C&?+and PKC alphasystems. Methods: immediately tier BDL, rats were fed UDCA or TUDCA (275 mmoliday) for 1 week. The number of ducts in liver sections, DNA synthesis and ductal secretionin isolatedcholangiocytes,were determined Then we evaluatedin bde duct cells the activity of UDCA andTUDCA on PKC, inhacellular C&2+ ([CaZ+]i) andapical bile acid transporta (ABAT) expression.Results: UDCA andTUDCA inbibitcd in viva cholangiocyte proliferative and secretiveprocesses. In vitro this inhibition require5 increased([Ca2+]1,PKC alphaand ABAT activity. Conclusions: UDCA andTUDCA inhibition of cholangiocytegmwtb and secretionis associatedwith BA uptakeby ABAT and increasedexpression of Cd+dependent PKC alpha.
51 ASSOCIATION IN PRIMARY
BILlARY CIRRHOSIS (PBC) A. Baragiotta,A. Floti, C. Venturi, P.T. Donaldson’, V. Bald@, M.F. Bassettdine*. Dept. of Surgicaland GarbmentemlogicalSciences,Uniwrsity of P&w, l Centrefor Liver Research,The Medical School,University of Newcastle uponTyne, UK, “Dept. of Public Health, University of Padova.
Universits.di Padova Intiwum: Ostiystmphy is amajor complicationof PBC, and its aetiology1smultifactorial. However, the r&tiombip behveenthe allelic polymorphism of the vitamin D receptor (VDR) gene, andbonemineral density hasbear repntcd in osteopomticsubjects from the generalpopulation, and,more recently in aNorth Americangroup ofPBC. Aims: I) To evaluateVDR gene polymorphism in PBC; 2) To identify the main risk factors for the developmentof bate loss. M&c& Eighty PBC patients(75 F, SM, median age49 years, range37-82.23 having histological stage I-n, 22 stageIII, and 35 stageIV) were comparedto IO0 sex- and agwnatched contmls from the samegeographicalarea A 740-base+ segmentof the VDR genewas amplified by standard PCRpmtowl, digestedwith restriction endonucleaseTaql, andresolved by gel electmphomsis. Alleles were classified as ‘T’ if only one TaqI site was p-t and“c” if two were present,and3 genotypesof theVTIR genewere identified: CC, CT, TT. Clinical information, bonemineral de&y (BMD) a.wessmentby dual-photonX-ray absmptiotnetryat the lumbar spine,Mayo score, menopausalstatus,were documented,and multivariateregressionanalysis~88 performed.Results: Thirty-four parent of PBC patientsbadosteoporosis(T-scorc;2.5). There was no statistical significant difference in the distribution of theVDR gas polymorphism in the PBC patients comparedto thecontrols (TT 33% vs 34%; CT 45% vs 46%; CC 22% vs 20%). However, CC genotypecarriers have amean BMD (0,668+0,15)andT-score (-2,833*1,35) significantly lower that thosewith TT genotype(BMD 0,91Mo,l2 andT-score -1,21+0,98),p