{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,13]],"date-time":"2025-12-13T19:05:10Z","timestamp":1765652710100,"version":"3.48.0"},"reference-count":33,"publisher":"BMJ","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Gut"],"published-print":{"date-parts":[[1993,1]]},"abstract":"<jats:p>Much research in the pathophysiology of gall stones has been devoted to various molecular species of bile salts. Recent findings have shown the importance of phospholipids in biliary pathophysiology. In the present study the addition of increasing doses of egg lecithin to human and model biles progressively prolonged the nucleation time. Concurrently biliary cholesterol was shifted from the vesicular to the non-vesicular carrier(s) while the cholesterol\/phospholipid ratio of the remaining vesicles was progressively lowered. Model bile solutions of identical lipid concentration were prepared using phosphatidylcholine, phosphatidylserine, and phosphatidylethanolamine as the only phospholipid. With phosphatidylethanolamine most of the cholesterol was shifted to the vesicular carrier while phosphatidylserine shifted most of the cholesterol to the non-vesicular carrier(s). With phosphatidylcholine the cholesterol was distributed in both carriers. Phosphatidyl choline species composed of various acyl fatty acids in the sn-1 and sn-2 positions were used as the sole phospholipid in otherwise identical model bile solutions. With palmitic acid in the sn-1 position and arachidonic acid in the sn-2 position most of the cholesterol was found in the non-vesicular carrier. When stearic acid was used in sn-2 position instead of arachidonic acid most of the cholesterol was found in the vesicular carrier. These and other variations in phospholipid molecular species shifted cholesterol among its carriers and also modified the nucleation time of model biles. Most of these effects were also found upon addition of the various phospholipid species to human biles. These findings show the importance of phospholipid species in biliary pathophysiology and may be useful when trying to manipulate cholesterol carriers and solubility in bile.<\/jats:p>","DOI":"10.1136\/gut.34.1.110","type":"journal-article","created":{"date-parts":[[2007,9,18]],"date-time":"2007-09-18T17:41:31Z","timestamp":1190137291000},"page":"110-115","source":"Crossref","is-referenced-by-count":30,"title":["Effect of phospholipids and their molecular species on cholesterol solubility and nucleation in human and model biles."],"prefix":"10.1136","volume":"34","author":[{"given":"Z","family":"Halpern","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M","family":"Moshkowitz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"H","family":"Laufer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Y","family":"Peled","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"T","family":"Gilat","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"239","published-online":{"date-parts":[[1993,1,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"998","DOI":"10.1172\/JCI109025","article-title":"The physical chemistry of cholesterol solubility in bile","volume":"61","author":"Carey, M.C.; Small, D.M.","year":"1978","unstructured":"Carey MC, Small DM. 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Contribution of micellar and vesicular carriers to cholesterol solubilitv in bile.] lzIipid Nc's"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1016\/0016-5085(79)90209-9","article-title":"Nucleation time: A key factor in the pathogenesis of cholesterol gallstone disease","volume":"77","author":"Holan, K.R.; Holzbach, R.T.; Hermann, R.E.; Cooperman, A.M.; Claffey, W.J.","year":"1979","unstructured":"Holan KR, Holzbach RT, Hermann RE, Cooperman AM, Claffey WJ. Nucleation time: A key factor in the pathogenesis of cholesterol gallstone disease. Gastroenterology 1979; 77:611-7.","journal-title":"Gastroenterology"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"924","DOI":"10.1016\/S0022-2275(20)40709-6","article-title":"Re-evaluation of the 3-hydroxysteroid dehydrogenase assay for total bile acids in bile","volume":"19","author":"Turlev, S.D.; Dietschy, J.M.","year":"1978","unstructured":"Turlev SD, Dietschy JM. 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Gastroenterol Int 1990; 3: 81-6.","journal-title":"Gastroenterol Int"},{"key":"ref_23","first-page":"825","article-title":"Influence of legume intake on biliary lipids and cholesterol","volume-title":"saturation in young Chilean men. Gastroenterology 1989; 96","author":"Nervi, F.; Cavarrubias, C.; Bravo, P.","unstructured":"Nervi F, Cavarrubias C, Bravo P, et al. Influence of legume intake on biliary lipids and cholesterol saturation in young Chilean men. Gastroenterology 1989; 96: 825-30."},{"key":"ref_24","first-page":"168","article-title":"Phospholipids in human hepatic bile, gall bladder bile and plasma in cases with acute cholecystitis. Scand3r Clin Lab Invest","volume":"21","author":"Gottfries, A.; Nilsson, S.; Samuelsson, B.; Schersten, T.","year":"1968","unstructured":"Gottfries A, Nilsson S, Samuelsson B, Schersten T. Phospholipids in human hepatic bile, gall bladder bile and plasma in cases with acute cholecystitis. Scand3r Clin Lab Invest 1968; 21: 168-76."},{"issue":"41","key":"ref_25","first-page":"361","article-title":"The lipid composition of human bile","volume":"1960","author":"Philips, G.B.","unstructured":"Philips GB. The lipid composition of human bile. Biochim Biophys Acta 1960; 41: 361.","journal-title":"Biochim Biophys Acta"},{"key":"ref_26","first-page":"1261","article-title":"Effect of dietarv cholesterol on phosphatidylcholines and phosphatidylethanolamines in bile and gallbladder mucosa","volume-title":"the prairie dog. Gastroenterology 1989; 97","author":"Booker, M.L.; Scott, T.E.; LaMorte, W.W.","unstructured":"Booker ML, Scott TE, LaMorte WW. Effect of dietarv cholesterol on phosphatidylcholines and phosphatidylethanolamines in bile and gallbladder mucosa in the prairie dog. Gastroenterology 1989; 97: 1261-7."},{"key":"ref_27","first-page":"599","article-title":"Molecular species of lecithins in human gallbladder bile: Hydrophilicity of the bile salt pool determines hydrophilicitv of the lecithins","volume":"10","author":"Hay, D.W.; Cahalane, M.J.; Timofeveva, N.; Carey, M.C.","year":"1989","unstructured":"Hay DW, Cahalane MJ, Timofeveva N, Carey MC. Molecular species of lecithins in human gallbladder bile: Hydrophilicity of the bile salt pool determines hydrophilicitv of the lecithins. Hepatology 1989; 10: 599.","journal-title":"Hepatology"},{"key":"ref_28","first-page":"404","article-title":"Molecular species of biliary phosphatidylcholines in gallstone patients: the influence of treatment with cholic acid and chenodeoxycholic acid. J7 Lipid","volume":"22","author":"Adlberg, J.; Curstedt, T.; Einarsson, K.; Sjovall, J.","year":"1981","unstructured":"Adlberg J, Curstedt T, Einarsson K, Sjovall J. Molecular species of biliary phosphatidylcholines in gallstone patients: the influence of treatment with cholic acid and chenodeoxycholic acid. J7 Lipid Res 1981; 22: 404-9.","journal-title":"Res"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1007\/BF02534904","article-title":"Structure of biliary phosphatidylcholine in cholesterol gallstone patients","volume":"16","author":"Cantafora, A.; Angelico, M.; DiBiase, A.; Pieche, U.; Bracci, F.; Attil, A.F.","year":"1981","unstructured":"Cantafora A, Angelico M, DiBiase A, Pieche U, Bracci F, Attil AF, et al. Structure of biliary phosphatidylcholine in cholesterol gallstone patients. Lipids 1981; 16: 589-92.","journal-title":"Lipids"},{"key":"ref_30","first-page":"236","article-title":"The alimentary production of gallstones in hamsters","volume":"30","author":"Dam, H.; Christensen, F.","year":"1952","unstructured":"Dam H, Christensen F. The alimentary production of gallstones in hamsters. Acta Pathol Microbiol Scand 1952; 30: 236-42.","journal-title":"Acta Pathol Microbiol Scand"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/0009-8981(87)90215-4","article-title":"Fatty acid composition of phospholipids in bile in man: promoting effect of deoxycholate on arachidonate","volume":"165","author":"GP, Van Berge Henegouwen; van der Werf SDJ; AT, Ruben","year":"1987","unstructured":"Van Berge Henegouwen GP, van der Werf SDJ, Ruben AT. Fatty acid composition of phospholipids in bile in man: promoting effect of deoxycholate on arachidonate. 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