Inhibition of 3α, 7α, 12α-trihydroxy-5β-cholestanoic acid (THCA) oxidation and of bile acid...
Transcript of Inhibition of 3α, 7α, 12α-trihydroxy-5β-cholestanoic acid (THCA) oxidation and of bile acid...
31 SERUM ANTIBODIES TO THYMUS EPITHELIAL CRIIA IN NON-A, NON-B (NANB) AND C R ~ I C CHRONIC LIVER DISEASE. F. CASSANI, F. ~LADA$, F.B. BIANC11I, L. BAFFONI, M. FUSCONII L. BENVEGNU*, M. LENZI, G. REALDI*, E. PISl. Istituto di Clinica Medica If, Cattedra di Semeiotiea Mediea, Universita' di Bologna and *Istituto di Medicina Clinica, Cattedra di Clinica Medica II, Universita' di Padova.
Antibodies reacting with both the basal cell layer (BCLA) of squamous epithelia and thy- mus epithelial cells (TEC) have been reported in 50% cases of HBV-HI)V chronic liver disease (CLD). Data are lacking on their occurrence in nAnB infection. Sere from 127 patients with various viral liver disorders, including prospectively diagnosed cases of nAnB post-tran- sfusion hepatitis, and from 26 patients with cryptogenic CLD without sert~n autoantibodies were tested by indirect IFL on cryostat sections of rat oesophagus and htmmn thymus.
nAnB nAnB HBsAg HBsAg cryptogenic HBV-HDV acute(32) chronic(35) acute(14) chronic(22) (26) chronic(24)
BCLA (1:40) 4(12%) 8(22%) 1 (7%) 1 (4%) 7(27%) 12(50%) anti TEC (I:i0) 4(12%) 15(43%) 4(29%) 4(18%) 11(42%) 12(50%) BCLA and anti TEC proved to be closely related (p<0.0001), although 23 of the 50 anti TEC positive sera were BCLA negative. On rat oesophagus and htmmu~ thymus a monoclonal antibody to cytokeratins n. 14,16,17 (Selavo) gave a pattern superimposable to that of spontaneous BCLA and anti TEC antibodies.
I. A common reactivity to cytokeratins is shared by beth BCLA and anti TEC. 2. The higher frequency of anti TEC maybe either due to a higher concentration of the antigen in thymus epithelium or to a broader spectrLBn of cytokeratins recognized by anti TEC. 3. This rectivity is widely distributed in all viral liver disorders, including nAnB infection. 4. Unlike in HBV infection, BCLA and anti TEC prevalence increases from the acute to the chronic phase in nAnB cases. 5. The close similarity between nAnB and cryptogenic CLD points to a nAnB etiology of a substantial proportion of cryptogenic CLD.
32 INHIBITION OF 3~, 7~, 12:-TRIHYDROXY-5B-CHOLESTANOIC ACID (THCA) OXIDATION AND OF BILE ACID SECRETION IN RAT LIVER BY FATTY ACIDS.
M. Casteels, L. Schepers, G. Parmentier* and G.P. Mannaerts. Afdeling Farmacolo- gie, Campus Gasthuisberg and *Rega Instituut, K.U.Leuven, B-3000 Leuven, Belgium
The B-oxidation of the side chain of THCA occurs mainly in peroxisomes, which are also capable of B-oxidizing fatty acids. (3,7,12-3H) and (26-14C)-THCA were synthetized and used to measure THCA activation and oxidation, respectively, and the influence of fat ty acids on these reactions was investigated. The oxidation, but not the uptake, of exogenous THCA was severely inhibited in isolated hepatocytes by medium- or long chain fat ty acids. THCA did not inhibi t fat ty acid oxidation. Also in l iver homogenates, an inhibi t ion of THCA activa- tion and oxidation by fat ty acids was observed. Competition experiments with THCA and fatty acids on the one hand and with the respective CoA ester on the other hand, strongly sugges- ted that the inhibit ion of THCA oxidation was actually the result of the inhibit ion of activation. The inhibit ion of activation was noncompetitive, indicating that THCA and fat ty acids may be activated by separate enzymes. Acyl-CoA oxidase, measured with palmitoyl-CoA as the substrate, was enhanced 15-fold in l iver homogenates of rats, treated with the peroxi- some prol i ferator clofibrate. The enzyme was not enhanced when the CoA ester of THCA was used as the substrate, suggesting that two separate oxidases may be involved in the peroxi- somal oxidation of fat ty acids and THCA. In the isolated perfused l iver , oleate, infused after a wash out period of 60 min, inhibited bi le acid secretion. The results l) demonstrate that fat ty acids inhibi t THCA metabolism and 2) suggest that fat ty acids may indirect ly af- fect bi le acid synthesis via their inhibitory effect on THCA metabolism.
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