Excretion INDEX

The smdy of tissue protein breakdown in vivo is difficult, because amino acids released during intracellular breakdown of proteins can be extensively reutilized for protein synthesis within the cell, or the amino acids may be transported to other organs where they enter anabohc pathways. However, actin and myosin are methylated by a posttranslational reaction, forming d-methylliistidine. During intracellular breakdown of actin and myosin, 3-methylhistidine is released and excreted into the urine. The urinary output of the methylated amino acid provides a rehable index of the rate of myofibrillar protein breakdown in the musculature of human subjects. 

Loft, S., Vistisen, K., Ewertz, M., Tjonneland, A., Overvad, K. and Poulsen, H.E. (1992). Oxidative DNA damage estimated by 8-hydroxydeoxyguanosine excretion in humans influence of smoking, gender and body mass index. Carcinogenesis 13, 2441-2447. 

Intestinal inflammation was assessed by fecal excretion of " In-labeled neutrophils while blood loss was quantitated via fecal excretion of 51Cr4abeled red cells. The urinary excretion ratio or51 Cr-EDTA//.-rhamnose was used as an index of intestinal permeability. ... 

The ability of the liver to act as a depot for vitamin Bi2 (B28, G13) enables us to use this vitamin as an index of proper hepatic function. Hepatic disorders lead to an increased Bi2-binding in the serum (J5, R3), suggesting that the blood assumes a greater role in the conservation of B12. We have reported that patients with liver disease excreted invariably less than 10 fig of Bi2> 8 hours after a 50-[ig intramuscular load dose of the vitamin. In contrast, normal subjects excreted 24-40 pg, i.e., 50-80% of the vitamin in the same test (B14). These results were correlated with various chemical determinations indicative of hepatic disorders (Bl). In Table 16 the clinical diagnosis and the various liver-... 

B14. Baker, H., Pasher, I., Dolger, H., and Sobotka, H., Vitamin B12 excretion as index of hepatic disorder. Clin. Chem. 2, 328-330 (1956). 

Alcohol consumption is very difficult to assess. There is widespread belief that individuals underreport their intake and there are no reliable laboratory tests available for definitive diagnosis of alcohol abuse. A combination of abnormalities in the plasma activity of gamma-glutamyl transferase (GGT or yGT), AST and reduction in erythrocyte mean cell volume (MCV) maybe useful and all are routine lab. tests. A potential marker of interest is carbohydrate-deficient transferrin (CDT) which is an abnormal isoform of serum transferrin arising due to defects in the attachment of carbohydrate chains to the protein core. Unfortunately, CDT is a somewhat specialized test, not performed by most laboratories. Other markers which have attracted some research interest are ethyl sulphate and ethyl glucuronide. Excretion in the urine of these metabolites occurs for up to 50 hours after binge drinking so they offer a useful index of recent heavy alcohol intake. 

Urinary excretion of total phenol (free and conjugates) is considered a biomarker of exposure for phenol. The biological exposure index (BEI) for phenol, for exposure to 5 ppm in air, is 250 mg/g creatinine when measured at the end of the shift (ACGIH 1991). 

Lithium is a drug with a narrow therapeutic index and therefore plasma concentrations are regularly monitored. Lithium is used in the prophylaxis and treatment of mania. Concurrent administration of lithium and diuretics, particularly the thiazides, is contraindicated as lithium excretion is reduced, resulting in increased plasma-lithium concentration and hence toxicity. 

In a study of workers engaged in synthesizing or otherwise handling p-dichlorobenzene, it was concluded that urinary excretion of 2,5-dichlorophenol (a metabolite of p-dichlorobenzene) can serve as an index of exposure."... 

Geriatric Considerations - Summary Increased risk of side effects in patients with CVD and hepatic dysfunction. Theophylline has a narrow therapeutic index and is associated with numerous drug interactions. Target serum concentrations are 5-20 mg/L, with adverse effects increasing between 15-20 mg/L. Hepatic metabolism and renal excretion declines with age and the half-life of theophylline increases by 3 to 9 hours in older adults. Smoking induces theophylline metabolism therefore, if a pa-tienf sfops smoking, empiric dosage reduction may be indicated and follow serum concenfrafions closely. 

Estriol (estra-1,3,5(10)-trien-3,16-a,17-8 -triol) is the major estrogen metabolite found in the urine. It is excreted in the form of its conjugate with glucuronic acid. The determination of this steroid as an index of placental function has become one of the most widely used endocrine determinations. As pregnancy progresses, the excretion increases and reaches very high levels near term. In abnormal fetoplacental function, the levels of estriol will fall in some cases. The fall is usually progressive, and, because of this, serial determinations of urinary estriol must be carried out. The drop in estriol can be taken as evidence of placental insufficiency, and close watch by the physician is indicated, as a continued drop may necessitate Cesarean section to save the life of the infant. 

Hepatic Effects. Exposure to 2,3,7,8-TCDD induces liver microsomal enzymes in both humans and animals, regardless of the route or duration of exposure. Increased urinary -glucaric acid (UGA) excretion, an indirect index of enzyme induction, was found in children with chloracne living in the Seveso area following the 1976 industrial accident (Ideo et al. 1982). Biochemical changes (increased... 

Table 8.1 represents some of the enzymes (Jakoby and Ziegler, 1990) that participate in altering xenobiotics so as to make them either more readily excretable or less toxic for the storage. These enzymes have a preference for lipophilic compounds, although all hydrophilic compounds, are not excluded. Each enzyme has a phenomenally broad substrate range, and many appear to be inducible. The information for xenometabolism can be obtained from the University of Minnesota Biocatalysis/Biodegradation Database (UM-BBD) at http //umbbd.ahc.umn.edu/ index.html (Ellis et al, 2000). 

Phenotypic trait measures based solely on the urinary excretion of 6-hydroxychlorzoxazone have also been reported based on the amount of metabolite excreted in zero to eight hours (278), or a hydroxylation index approach (279), or estimating the elimination half-life of the metabolite (280). However, the validity of these approaches is highly questionable, so they have not been widely applied. 

Dreisbach AW, Ferencz N, Hopkins NE, et al. Urinary excretion of 6-hydroxychlorzoxazone as an index of CYP2E1 activity. Clin Pharmacol Ther 1995 58 498-505. 

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