Plasma bile acids

Driscoll TR, Hamdan HH, Wang G, et al. 1992. Concentrations of individual serum or plasma bile acids in workers exposed to chlorinated aliphatic hydrocarbons. Br J Ind Med 49 700-705. 

Stellaard F, Langelaar SA, Kok RM, Jakobs C (1989) Determination of plasma bile acids by capillary gas-liquid chromatography-electron capture negative chemical ionization mass fragmentography. J Lipid Res 30 1647-1652... 

Of the systems listed in Table VI, melphalan is most stable in the Burroughs-Wellcome injectable kit. The instructions recommend the use of the solution within 15—30 minutes. According to the manufacturer, 8.5% hydrolysis takes place in 24 hours after mixing [86]. The stability of melphalan increases in acidic solutions and higher temperatures accelerate the hydrolysis. The type and concentration of anionic species present in the solution alter the hydrolysis rate. The formation of the intermediate ionized species is retarded and/or reversed by the presence of chloride ions [9,82,87], resulting in a significantly increased stability [53,87,88]. The stability of melphalan is increased in the presence of bovine serum albumin, human plasma, bile acids, and bile, probably by hydrophobic interactions that make the chloroethyl moiety less accessible to nucleophilic attack [40,62,74,87,89—91]. 

Disturbances of Bile Acid Metabolism in Hepatocellular Disease. Fasting plasma bile acid concentrations are elevated in hepatocellular diseases, such as hepatitis and cirrhosis. The mechanisms responsible are regurgitation of bile acids from cholestatic hepatocytes and portosystemic shunting. These defects allow the plasma concentrations to rise proportionately much higher than normal following meals, suggestmg that the postprandial rise in plasma bile acids may be a sensitive test for the detection of liver disease. 

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. 

Sjovall, J. and Sjovall, K. (1970) Steroid sulphates in plasma from pregnant women with pruritus and elevated plasma bile acid levels. Annals of Clinical Research, 2 (4), 321-337. 

Either plasma total bilirubin or plasma bile acids should be measured, but these are different measurements. Bile acids are more of a functional assay that is subject to more variation, particularly following food intake. 

Plasma bile acids (total bile acids, TBAs) have been recommended as an alternative measurement to plasma bilirubin because TBAs can indicate biliary functionality in terms of the response to food intake. TBA values are dependent upon a number of factors, including stomach emptying gall bladder contraction, where it exists intestinal motility intestinal absorption hepatic uptake and hepatic excretion. The enterohepatic circulation amplifies deficiencies in the hepatic transport system this results in reduced secretion of bile acids into the bile. Studies with dogs have shown that timed postprandial measurements have greater diagnostic value than fasting or random samples (Center et al. 1991 Jensen and Poulsen 1992), but the collection of timed postprandial samples is more difficult. 

Profiling of elevated plasma coneentrations of bile acids provides evidence of functional inhibition of bile salt clearance in vivo. This has been observed in rats exposed to a variety of drugs that inhibit BSEP activity in vitro, and in some instances also in humans (Fattinger et al., 2001), which snggests that evalnation of plasma (or serum) bile acids could provide a useful noninvasive biomarker of in vivo BSEP inhibition. However, since uptake carriers on the basolateral plasma membrane domain mediate hepatic nptake of bile acids and therefore also play important roles in bile acid clearance (Kullak-Ublick et al., 2004), potential interactions involving these transporters need to be considered when interpreting effects of compounds on plasma bile acid concentrations. In addition, elevated bile acid concentrations have been observed in plasma and urine from rats treated in vivo with a variety of hepatotoxic drugs, some of which do not inhibit BSEP (e.g., acetaminophen, carbam-azepine Yamazaki et al., 2013). Therefore while elevated total plasma bile acid levels can provide a nseful indirect index of impaired in vivo BSEP-mediated bile salt clearance, they may also arise due to other mechanisms and so cannot be considered a specific in vivo BSEP inhibition biomarker. 

By swabbing the skin of the the back with cotton wool moistened with acetone, Schoenfield et al. (125) obtained an extract that was analyzed for bile acids with the methods described above for human plasma bile acids (31). 

A Simplified Gas-Liquid Chromatographic Method for the Estimation of Non-sulfated Plasma Bile Acids... 

Oxo-A -bile acids constitute >10% of total plasma bile acids. 

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