Bile acids measurement

High-throughput assay of bile acids is technically demanding and expensive. Combined with high intra- and inter-individual variability in stool bile acid levels, it is unlikely that bile acid measurement will find a role as a biomarker of future colorectal neoplastic risk. 

In vivo, measuring bile acids in plasma and urine should be revived as potential biomarkers in the modern metabolomic era. Then the first-order scientific question will become whether early and time-controlled fasting-level measurement of bile acid concentration in plasma and urine can become a sensitive and specific biomarker for drug-induced cholestasis and ultimately liver injury at later time-points [117] Clinical trials should be conducted to evaluate whether such bile acid measurements can be used as part of a predictive panel to identify patients who are at increased risk of drug-induced cholestasis. 

Increased plasma bile acid concentrations in the fasting state suggest impaired hepatic uptake or secretion, or portosystemic shunting. Thus, such measurements may be used as a sensitive endogenous clearance test. However, a diagnosis suggested by an increase in plasma bile acid concentrations should be confirmed by standard liver function tests. In a similar manner, abnormal standard liver function tests can be confirmed as indicative of hepatic dysfunction by concomitant measurement of plasma bile acids. Plasma bile acid measurements may also be used serially to monitor patients with suspected or proven hepatic disease. However, they add little to standard tests of hver function and are now rarely used in clinical medicine. 

Skrede, S., Solberg, H. E., Blomhoff, J. P., and Gjone, E., Bile acids measured in serum during fasting as a test for liver disease. Clin. Chem. (Winston-Salem, N.C.) 24, 1095-1099 (1978). 

Serum cholesterol is usually markedly elevated in biliary obstruction, with especially high values in biliary cirrhosis. A positive correlation is found occasionally (196) but not constantly (193) between the serum bile acid and cholesterol levels. An absence of bile acids in the gut lumen and a reduced cholesterol absorption may stimulate, at least initially, both intestinal and hepatic cholesterol production cf. 92,223), and this in association with a block in elimination both as bile acids and as cholesterol itself rapidly raises the serum cholesterol level. However, in biliary obstruction of long duration, e.g., in biliary cirrhosis, sterol balance studies and urinary bile acid measurement indicate that cholesterol synthesis is markedly reduced (88). In parenchymal cell damage of the liver, the serum cholesterol is normal or decreased, probably because the hepatic cholesterol synthesis, due to cell injury, is reduced in proportion to, or proportionally more than, the decreased cholesterol elimination (11,182) and, furthermore, intestinal and hepatic cholesterogenesis may still be under the partial feedback control of bile acids and absorbed cholesterol, respectively. 

Cholesterol, plant sterols, and bile acids Measurements of cholesterol and plant sterols in plasma and lymph are obtained by GC, but HPLC has also gained in importance as a method of sensitive... 

X = tendon xanthomata, H = homozygous, M = mother, F = father second values after cholestyramine treatment. include fecal bile acids of chenodeoxycholic acid origin values collected from ref. 25-34 bile acids measured in, 22 subjects Two present cases and patients from ref. 26,28,29.°Mainly from... 

Clinical Analysis. A wide range of clinically important substances can be detected and quantitated using chemiluminescence or bioluminescence methods. Coupled enzyme assay protocols permit the measurement of kinase, dehydrogenase, and oxidases or the substrates of these enzymes as exemplified by reactions of glucose, creatine phosphate, and bile acid in the following ... 

Solubility and dissolution are processes that take place in the gastric and the luminal fluids, not on the surface of epithelial cells. Measurement of solubility ideally needs to take place at pH 1.7 (stomach) and pH 5-8 (small intestinal tract). Ideally, the screen media should resemble intestinal fluids and contain bile acid-lecithin mixed micelles. Fast and reliable techniques for assessing solubility in... 

The answer is a. (Hardman, pp 885-8870 Lovastatin should not be used in patients with severe liver disease. With routine use of lovastatin, serum transaminase values may rise, and in such patients the drug may be continued only with great caution. Lovastatin has also been associated with lenticular opacities, and slit-lamp studies should be done before and one year after the start of therapy There is no effect on the otic nerve. The drug is not toxic to the renal system, and reports of bone marrow depression are very rare There is a small incidence of myopathy, and levels of creatinine kinase should be measured when unexplained muscle pain occurs. Combination with cyclosporine or clofibrate has led to myopathy There is no danger in use with bile acid sequestrants. 

Studies in experimental animals suggest that biliary excretion of chemicals from the liver may be impaired by mirex or chlordecone (Berman et al. 1986 Curtis and Hoyt 1984 Curtis and Mehendale 1979 Curtis et al. 1979b, 1981 Davison et al. 1976 Mehendale 1976, 1977b, 1977c, 1981b Teo and Vore 1991). Measurement of serum bile acid levels may provide information regarding biliary excretory function. 

Although both LDL and HDL are primarily cholesterol particles, most of the cholesterol measured in the blood is assodated with LDL. The normal role of LDL is to deliver cholesterol to tissues for biosynthesis. When a cell is repairing membrane or dividing, the cholesterol is required for membrane synthesis. Bile acids and salts are made from cholesterol in the liver, and many other tissues require some cholesterol for steroid synthesis. As shown in Figure 1-15-6, about 80% of LDL are picked up by hepatocytes, the remainder by peripheral tissues. ApoB-100 is the only apoprotein on LDL, and endocytosis of LDL is mediated by apoB-100 receptors (LDL receptors) clustered in areas of cell membranes lined with the protdn clathrin. 

The aggregation behavior of C21-DA salt in dilute electrolyte medium appears to resemble that of certain polyhydroxy bile salts (25,16). That C21-DA, with a structure quite different from bile acids, should possess solution properties similar to, e.g., cholic acid is not entirely surprising in light of recent conductivity and surface tension measurements on purified (i.e., essentially monocarboxylate free) disodium salt aqueous solutions, and of film balance studies on acidic substrates (IX) The data in Figure 3 suggest that C21-DA salt micelles Incorporate detergents - up to an approximate weight fraction of 0.5 -much like cholate Incorporates lecithin or soluble... 

Micelles tend to aggregate, and there are many ways to measure their concentration, including surface tension measurements. The midpoint of the concentration range over which micellar aggregation occurs is called the critical micellar concentration (CMC). Below the CMC, added bile-salt molecules dissolve in the form of monomers above the CMC, added bile-salt molecules form micelles, leaving the monomeric concentration essentially constant. The pH at which CMC formation occurs is called the critical micellar pH, (CMpH). Table 1.1 lists values for some of the bile acids mentioned in this review. 

The most common assay uses 3a-hydroxysteroid dehydrogenase to form the 3-keto bile acid that is trapped by, for example, hydrazine hydrate, causing the reaction to go to completion. The co-factor NAD is reduced stoichiometrically and can be measured by ultraviolet absorption or more commonly by fluorescence at an activation of 345 nm and emission of 450 nm. Use of this enzyme measures all bile acids with a 3a-hydroxyl but not cholesterol, which has a 3p-hydroxyl, and does not measure bile acids with a sulphate or glucuronide group conjugated to the 3a-hydroxyl. 

Assays have also made use of 7a-hydroxysteroid dehydrogenase that can measure the primary bile acids, or for more specialised purposes such as differentiating between pathways of bile-acid synthesis to determine the proportion derived from the acid pathway. 

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