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1.
Handb Exp Pharmacol ; 256: 237-264, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31236688

RESUMEN

Bile acids (BAs) are key molecules in generating bile flow, which is an essential function of the liver. In the last decades, there have been great advances in the understanding of BA physiology, and new insights have emerged regarding the role of BAs in determining cell damage and death in several liver diseases. This new knowledge has helped to better delineate the pathophysiology of cholestasis and the adaptive responses of hepatocytes to cholestatic liver injury as well as of the mechanisms of injury of biliary epithelia. In this context, therapeutic approaches for liver diseases using hydrophilic BA (i.e., ursodeoxycholic acid, tauroursodeoxycholic, and, more recently, norursodeoxycholic acid), have been revamped. In the present review, we summarize current experimental and clinical data regarding these BAs and its role in the treatment of certain liver diseases.


Asunto(s)
Hepatopatías/tratamiento farmacológico , Ácido Tauroquenodesoxicólico/farmacología , Ácido Ursodesoxicólico/análogos & derivados , Ácido Ursodesoxicólico/farmacología , Ácidos y Sales Biliares , Colestasis , Humanos , Hígado
2.
Hepatology ; 23(6): 1402-11, 1996 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-8675157

RESUMEN

To evaluate the a priori hypotheses that an increased level of glyco and tauro lithocholic acid, perhaps because of a decreased capacity for hepatic sulfation, contributed to the biochemical epidemiology of gallbladder cancer, a case-control study was undertaken at four hospitals in La Paz, Bolivia, and at one hospital in Mexico City, Mexico. Eighty-four cases with newly diagnosed histologically confirmed gallbladder cancer were compared with 264 controls with cholelithiasis or choledocholithiasis in the absence of cancer and with 126 controls with normal biliary tracts. All study subjects were undergoing abdominal surgery. Interview data were collected for all study subjects, as well as blood, bile, and gallstone specimens when feasible. Sera were analyzed for carcinoembryonic antigen, cholesterol concentration, and total bile acids. Bile specimens were analyzed for carcinoembryonic antigen; and for concentration of bile salts; cholesterol; phospholipids; and the glycine and taurine conjugates of cholic, ursodeoxycholic, chenodeoxycholic, deoxycholic, and lithocholates; sulfoglycolithocholate; and sulfotaurolithocholate. Gallstone specimens were analyzed for the percentage of cholesterol content, the percentage of calcium bilirubinate content, and the percentage of calcium carbonate content. Serum bile acids were increased in cases versus the two control groups (median 11.7 nmol/mL vs. 9.3 nmol/mL for stone controls and 8.2 nmol/L for nonstone controls, P < or = .02 for each pairwise comparison). Biliary bile acids were markedly decreased in the cases (median 3.98 micromol/mL vs. 33.09 micromol/mL, and 154.0 micromol/L, respectively, P < or = .0001 for each comparison), even after excluding those with a serum bilirubin higher than 2.0 mg/dL. Bile cholesterol was lower for the cases as well (median 1.70 micromol/mL vs. 4.90 micromol/mL, and 16.81 micromol/ mL, respectively, P < or = .02), as was the concentration of bile phospholipids (median 2.97 micromol/mL vs. 6.26 micromol/mL, and 52.69 micromol/mL, P = .1 and .0004, respectively). Contrary to our a priori hypothesis, there was no difference between the cases and either control group in their bile concentrations of lithocholate, the proportion of bile acids which were sulfated, or the concentration of nonsulfated lithocholate. However, the cases had a higher concentration of ursodeoxycholate (UDC) (P < .004 for both control groups), especially glycoursodeoxycholate (P < .001 for both control groups). A previously published suggestion that gallstone size differed between cases and controls was not confirmed. In conclusion, cases with gallbladder cancer differed from controls with stones and from controls with normal biliary tracts in their serum and bile biochemistries. These findings may be a reflection of the disease process, or may provide useful clues to its pathogenesis.


Asunto(s)
Neoplasias de la Vesícula Biliar/epidemiología , Neoplasias de la Vesícula Biliar/metabolismo , Adulto , Anciano , Bilis/metabolismo , Ácidos y Sales Biliares/sangre , Ácidos y Sales Biliares/metabolismo , Bilirrubina/sangre , Bolivia/epidemiología , Estudios de Casos y Controles , Colelitiasis/complicaciones , Colelitiasis/metabolismo , Femenino , Neoplasias de la Vesícula Biliar/etiología , Cálculos Biliares/complicaciones , Cálculos Biliares/metabolismo , Humanos , Ácido Litocólico/metabolismo , Masculino , México/epidemiología , Persona de Mediana Edad , Sulfatos/metabolismo , Ácido Ursodesoxicólico/análogos & derivados , Ácido Ursodesoxicólico/metabolismo
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