Importance of Bile Composition for Diagnosis of Biliary Obstructions

Determination of the cause of a biliary obstruction is often inconclusive from serum analysis alone without further clinical tests. To this end, serum markers as well as the composition of bile of 74 patients with biliary obstructions were determined to improve the diagnoses. The samples were collected from the patients during an endoscopic retrograde cholangiopancreatography (ERCP). The concentration of eight bile salts, specifically sodium cholate, sodium glycocholate, sodium taurocholate, sodium glycodeoxycholate, sodium chenodeoxycholate, sodium glycochenodeoxycholate, sodium taurodeoxycholate, and sodium taurochenodeoxycholate as well as bile cholesterol were determined by HPLC-MS. Serum alanine aminotransferase (ALT), aspartate transaminase (AST), and bilirubin were measured before the ERCP. The aim was to determine a diagnostic factor and gain insights into the influence of serum bilirubin as well as bile salts on diseases. Ratios of conjugated/unconjugated, primary/secondary, and taurine/glycine conjugated bile salts were determined to facilitate the comparison to literature data. Receiver operating characteristic (ROC) curves were determined, and the cut-off values were calculated by determining the point closest to (0,1). It was found that serum bilirubin was a good indicator of the type of biliary obstruction; it was able to differentiate between benign obstructions such as choledocholithiasis (at the concentration of >11 µmol/L) and malignant changes such as pancreatic neoplasms or cholangiocarcinoma (at the concentration of >59 µmol/L). In addition, it was shown that conjugated/unconjugated bile salts confirm the presence of an obstruction. With lower levels of conjugated/unconjugated bile salts the possibility for inflammation and, thus, neoplasms increase.

ESR Spectroscopy Insight on the Anticancer Drug Mitoxantrone Location in Membrane Mimetic Systems

The location of mitoxantrone molecule in micelles formed by bile salts (sodium taurocholate (NaTC) and sodium taurodeoxycholate (NaTDC)) and sodium dodecyl sulfate (SDS) have been investigated by electron spin resonance (ESR) spectroscopy, using three doxylstearic acid probes (5-, 12- and 16-doxylstearic acid abbreviated as 5-DSA, 12-DSA and 16-DSA). The analysis of ESR parameters of these spin probes evidenced slower dynamics induced by mitoxantrone that vary in the following order: 12-DSA > 5-DSA > 16-DSA for both bile salts micelles and 5-DSA > 12-DSA > 16-DSA for SDS micelles. The ESR parameters are slightly sensitive to variation of pH. These results indicate that the spin probes target different regions in these aggregates. Keywords: mitoxantrone, bile salts micelles, SDS micelles, ESR spectroscopy