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1. Sandler R. S., Everhart J. E., Donowitz M. et al. The burden of selected digestive diseases in the United States // Gastroenterology. 2002 May; 122 (5): 15001511.
2. : . . . . . . .: . -, 2002. 416 .
3. . . .: -, 2001. 264 .
4. Sun H., Tang H., Jiang S. et al. Gender and metabolic differences of gallstone diseases // World J Gastroenterol. 2009, April 21; 15 (15): 18861891.
5. Schirmer B. D., Edlich R. F., Winters K. L. Cholelithiasis and Cholecystitis // J Long Term Eff MedImplants. v15.i3.90.
6. Everhart J. E., Khare M., Hill M., Maurer K. R. Prevalence and ethnic differences in gallbladder disease in the United States // Gastroenterology. 1999; 117: 632639.
7. Russo M. W., Wei J. T., Thiny M. T. et al. Digestive and liver diseases statistics, 2004//Gastroenterology. 2004; 126: 14481453.
8. . ., . ., . . . . 2010, surgery.ru.
9. Marschall H.-U., Einarsson C. Gallstone disease // Journal of Internal Medicine. 2007; 261: 529542.
10. Dowling R. H. Review: pathogenesis of gallstones // Aliment Pharmacol Ther. 2000; 14 (Suppl): 3947.
11. Chiang J. Y., Kimmel R., Stroup D. Gene. Regulation of cholesterol 7 alpha-hydroxylase gene (CYP7 A1) transcription by the liver orphan receptor (LXRalpha). 2001; 10; 262 (12): 257265.
12. Twisk J., Hoekman M. F., Mager W. H. et al. Heterogeneous expression of cholesterol 7 alpha-hydroxylase and sterol 27-hydroxylase genes in the rat liver lobulus // J Clin Invest. 1995; 95: 12351243.
13. Groothuis G. M., Hardonk M. J., Keulemans K. P. et al. Autoradiographic and kinetic demonstration of acinar heterogeneity of taurocholate transport // Am J Physiol Gastrointest Liver Physiol. 1982; 243: G455G462.
14. Russell D. W. The enzymes, regulation, and genetics of bile acid synthesis // Annu Rev Biochem. 2003; 72: 137174.
15. Chiang J. Y. Regulation of bile acid synthesis: pathways, nuclear receptors, and mechanisms //J Hepatol. 2004; 40: 539551.
16. Makishima M., Okamoto A. Y., Repa J. J. et al. Identification of a nuclear receptor for bile acids // Science. 284: 13621365.
17. Parks D. J., Blanchard S. G., Bledsoe R. K. et al. Bile acids: natural ligands for an orphan nuclear receptor // Science. 284: 13651368.
18. Wang H., Chen J., Hollister K. et al. Endogenous receptor FXR/BAR // Mol Cell. 3: 543553.
19. Lefebvre P., Cariou B., Lien F. et al. Role of Bile Acids and Bile Acid Receptors in Metabolic Regulation // Physiol Rev. 2009; 89: 147191.
20. Alrefai W. A., Gill R. K. Bile acid transporters: structure, function, regulation and pathophysiological implications // Pharm Res. 2007; Oct; 24 (10): 18031823.
21. Trauner M., Claudel T., Fickert P. et al. Bile acids as regulators of hepatic lipid and glucose metabolism // Dig Dis. 2010; 28 (1): 220224.
22. Houten S. M., Watanabe M., Auwerx J. New EMBO Members Review. Endocrine functions of bile acids // The EMBO Journal. Vol 25 (7): 14191425.
23. Watanabe M., Houten S. M., Mataki C. et al. Bile acids induce energy expenditure by promoting intracellular thyroid hormone activation // Nature 2006; 439: 484489.
24. Fiorucci S., Mencarelli A., Palladino G., Cipriani S. Bile-acid-activated receptors: targeting TGR5 and farnesoid-X-receptor in lipid and glucose disorders // Trends Pharmacol Sci. 2009; 30 (11): 570580.
25. Ke Ma, Pradip K. Saha et al. Farnesoid X receptor is essential for normal glucose homeostasis // J. Clin. Invest. 2006; 116: 11021109.
26. Chiang J. Y. L. Bile Acid Regulation of Hepatic Physiology III. Bile acids and nuclear receptors // Am J Physiol Gastrointest Liver Physiol. 2003; 284: G349G356.
27. Mendez-Sanchez N., Chavez-Tapia N. C., Motola-Kuba D. et al Metabolic syndrome as a risk factor for gallstone disease // World J Gastroenterol. 2005; 11 (11): 16531657.
28. Liu C. M., Tung T. H., Liu J. H. et al. A communitybased epidemiologic study on gallstone disease among type 2 diabetics in Kinmen, Taiwan // Dig Dis. 2004; 22: 8791.
29. De Santis A., Attili A. F., Ginanni Corradini S. et al. Gallstones and diabetes: a case-control study in a free-livingpopulation sample // Hepatology. 1997; 25: 787790.
30. Kim J. M., Lee H. L., Moon W. et al. Association between insulin, insulin resistance, and gallstone disease in Korean general population // Korean J Gastroenterol. 2007, Sep; 50 (3): 183187.
31. Mendez-Sanchez N., Bahena-Aponte J.,Chavez-Tapia N. C. et al. Strong association between gallstones and cardiovascular disease //Am J Gastroenterol. 2005, Apr; 100 (4): 827830.
32. Chen C. H., Huang M. H., Yang J. C. et al. Prevalence and risk factors of nonalcoholic fatty liver disease in an adult population of taiwan: metabolic significance of nonalcoholic fatty liver disease in nonobese adults // J Clin Gastroenterol. 2006, Sep; 40 (8): 745752.
33. . ., . ., . ., . . -: , . http://www.rmj.ru.
34. . . : // . . ., ., . 1994; . IV, 4. . 625.
35. Berger M. Y., van der Velden J. J., Lijmer J. G. et al. Abdominal symptoms: do they predict gallstones A systematic review Scand // J. Gastroenterol. 2000; Vol. 35. P. 7076.
36. Field A. E., Coakley E. H., Must A. et al. Impact of overweight on the risk of developing common chronic diseases during a 10-year period // Arch. hitem. Med. 2001. Vol. 161. P. 15811586.
37. Hofmann A. F. The continuing importance of bile acids in liver and intestinal disease //Arch Intern Med. 1999, Dec 1327;159 (22): 26472658.
38. Wagner M., Trauner M. Transcriptional regulation of hepatobiliary transport systems in health and disease: implications for a rationale approach to the treatment of intrahepatic cholestasis // Ann Hepatol. 2005 Apr-Jun; 4 (2): 7799.
39. Gilat T., Leikin-Frenkel A., Goldiner I. et al. Dissolution of Cholesterol Gallstones in Mice by the Oral Administration of a Fatty Acid Bile Acid Conjugate // Hepatology. 2002, Vol. 35, 3: 597600.
40. . ., . ., . . . .: , 2008.
41. Mudipalli A. // Indian J Med Res. 2007, 126: 518527.
42. . . . www.pharmateca.ru.