In bile

Two nucleation processes important to many people (including some surface scientists ) occur in the formation of gallstones in human bile and kidney stones in urine. Cholesterol crystallization in bile causes the formation of gallstones. Cryotransmission microscopy (Chapter VIII) studies of human bile reveal vesicles, micelles, and potential early crystallites indicating that the cholesterol crystallization in bile is not cooperative and the true nucleation time may be much shorter than that found by standard clinical analysis by light microscopy [75]. Kidney stones often form from crystals of calcium oxalates in urine. Inhibitors can prevent nucleation and influence the solid phase and intercrystallite interactions [76, 77]. Citrate, for example, is an important physiological inhibitor to the formation of calcium renal stones. Electrokinetic studies (see Section V-6) have shown the effect of various inhibitors on the surface potential and colloidal stability of micrometer-sized dispersions of calcium oxalate crystals formed in synthetic urine [78, 79]. 

Florfenicol has a wide tissue distribution, similar to that reported for chloramphenicol in calves and thiamphenicol in humans (43,44). Chloramphenicol attains concentrations higher than the corresponding plasma concentrations in bile and urine, as does florfenicol (43). Unlike florfenicol, chloramphenicol concentrations in the Hver, kidney, spleen, and lungs are less than corresponding plasma concentrations. However, chloramphenicol penetrates the brain and CSF much better than does florfenicol, reaching values equal to plasma concentrations in the brain. The distribution of thiamphenicol into the kidney, urine, and muscles of humans compared with corresponding plasma concentration is similar to what was observed for florfenicol in calves (44). The penetration of thiamphenicol into the CSF is much smaller than that of florfenicol in calves. 

The kidney is an important organ for the excretion of toxic materials and their metaboHtes, and measurement of these substances in urine may provide a convenient basis for monitoring the exposure of an individual to the parent compound in his or her immediate environment. The Hver has as one of its functions the metaboHsm of foreign compounds some pathways result in detoxification and others in metaboHc activation. Also, the Hver may serve as a route of elimination of toxic materials by excretion in bile. In addition to the Hver (bile) and kidney (urine) as routes of excretion, the lung may act as a route of elimination for volatile compounds. The excretion of materials in sweat, hair, and nails is usually insignificant. 

Decalin ring systems appear as structural units in a large number of naturally occurring substances, particularly the steroids. Cholic acid, for example, a steroid present in bile that promotes digestion, incorporates d5-decalin and rran -decalin units into a rather complex tetracyclic structure. 

C27H45OH, crystallising in the form of acicular crystals and found in all animal fats and oils, in bile, blood, brain tissue, milk, yolk of egg, the medullated sheaths of nerve fibres, the liver, kidneys and adrenal glands. 

CYP27A1 catalyzes the side chain oxidation (27-hydroxylation) in bile acid biosynthesis. Because bile acid synthesis is the only elimination pathway for cholesterol, mutations in the CYP27A1 gene lead to abnormal deposition of cholesterol and cholestanol in various tissues. This sterol storage disorder is known as cerebrotendinous xanthomatosis. CYP27B1 is the 1-alpha hydroxylase of vitamin D3 that converts it to the active vitamin form. The function of CYP27C1 is not yet known. 

Enterohepatic circulation can lead to toxic effects. For example, the drug chloramphenicol is metabolized to a conjugate that is excreted in bile by the rat. Once in the gut, the conjugate is broken down to release a phase 1 metabolite that undergoes further metabolism to yield toxic products. When these are reabsorbed, they can cause toxicity. The rabbit, by contrast, excretes chloramphenicol conjugates in urine, and there are no toxic effects at the dose rates in question. 

Gibson, R., Smith, M.D., and Spary, C.J. et al. (2005). Mixtures of estrogenic contaminants in bile of fish exposed to wastewater treatment works effluents. Environmental Science and Technology 39, 2461-2471. 

The enzymes in peroxisomes do not attack shorter-chain fatty acids the P-oxidation sequence ends at oc-tanoyl-CoA. Octanoyl and acetyl groups are both further oxidized in mitochondria. Another role of peroxisomal P-oxidation is to shorten the side chain of cholesterol in bile acid formation (Chapter 26). Peroxisomes also take part in the synthesis of ether glycerolipids (Chapter 24), cholesterol, and dolichol (Figure 26-2). 

Stocker, R and Ames, B. (1987). Potential role of conjugated bilirubin and copper in the metabolism of lipid peroxides in bile. Proc. Natl Acad. Sci. USA 84, 8130-8134. 

Craven, P.A., Pfanstiel, J. and DeRubertis, F.R. (1986). Role of reactive oxygen in bile salt stimulation of colonic epithelial proliferation. J. Clin. Invest. 77, 850-859. 

Mechref, Y., Chen, P, and Novotny, M. V., Structural characterization of the N-linked oligosaccharides in bile salt-stimulated lipase originated from human breast milk, Glycobiology, 9, 227, 1999. 

Bile acids The organic acids in bile contains sodium glycocholate and sodium taurocholate, cholesterol, biliverdin and bilirubin, mucus, fat, lecithin, and cells and cellular debris. 

Based on the data from animal studies, diisopropyl methylphosphonate is principally excreted in the urine as the metabolite IMPA (Hart 1976 Ivie 1980). Chromatographic behavior of urinary metabolites does not change after the urine is treated with glucuronidase and sulfatase, so there is no conjugation of diisopropyl methylphosphonate or IMPA by microsomal enzymes (Hart 1976). There was minimal excretion of diisopropyl methylphosphonate metabolites in bile (Hart 1976) or in the milk of a lactating cow (<1%) (Palmer et al. 1979). 

Despite the bad press, the body needs cholesterol. In fact, cholesterol is a key ingredient in bile. The more bile the body makes, the lower the amount of cholesterol in the bloodstream. 

Drug absorption is highly variable in neonates and infants [21,22]. Older children appear to have absorption patterns similar to adults unless chronic illness or surgical procedures alter absorption. Differences in bile excretion, bowel length, and surface area probably contribute to the reduced bioavailability of cyclosporine seen in pediatric liver transplant patients [22a]. Impaired absorption has also been observed in severely malnourished children [22b]. A rapid GI transit time may contribute to the malabsorption of carbamazepine tablets, which has been reported in a child [23]. Selection of a more readily available bioavailable dosage form, such as chewable tablets or liquids, should be promoted for pediatric patients. 

B Lund, JP Kampmann, F Lindahl, MJ Hansen. Pivampicillin and ampicillin in bile, portal and peripheral blood. Clin Pharmacol Ther 19 587-591, 1976. 

Baker et al. [138] studied the excretion of metabolites in bile following the administration of primaquine in rats. Six metabolites of primaquine were found in the bile of rats. Quantitative high performance liquid chromatography analysis of the metabolites revealed that the sum of the six metabolites excreted in the bile represented quantitative recovery of the dose of primaquine. 

Since animal data indicated the presence of an entero-hepatic circulation [59], the biliary concentration of rifaximin after oral preoperative administration of the drug (400 mg every 12 h) was evaluated in bile samples taken from patients undergoing cholecystectomy [106]. In 7 out... 

Adults require 1-2 mg of copper per day, and eliminate excess copper in bile and feces. Most plasma copper is present in ceruloplasmin. In Wilson s disease, the diminished availability of ceruloplasmin interferes with the function of enzymes that rely on ceruloplasmin as a copper donor (e.g. cytochrome oxidase, tyrosinase and superoxide dismutase). In addition, loss of copper-binding capacity in the serum leads to copper deposition in liver, brain and other organs, resulting in tissue damage. The mechanisms of toxicity are not fully understood, but may involve the formation of hydroxyl radicals via the Fenton reaction, which, in turn initiates a cascade of cellular cytotoxic events, including mitochondrial dysfunction, lipid peroxidation, disruption of calcium ion homeostasis, and cell death. 

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