In human tissues

The dmg is readily absorbed from the gastrointestinal tract and may persist in human tissues for two months after adrninistration. Quinacrine is given as a single dose for the treatment of tapeworms it is manufactured by Winthrop-Breon of New York, New York. 

J. B. Wheatley, J. A. Montali and D. E. Schmidt-Jr, Coupled affinity-reversed-phase high-performance liquid cliromatography systems for the measurement of glutathione 5-transferases in human tissues , 7. Chromatogr. A 676 65 - 79 (1994). 

The quantification of kinins in human tissues or body fluids has been limited due to the inherent difficulties in accurately measuring the concentration of ephemeral peptides. Today HPLC-based and RIA/capture-ELA measurements are established to determine kinins in human plasma, liquor or mine. Serine protease inhibitors need to be added to prevent rapid degradation of the kinins in vitro during sample preparation. Kinins and their degradation products have been studied in various biological milieus such as plasma/ serum, urine, joint fluids, kidney, lung and skeletal muscle [2]. Under normal conditions, the concentration of kinins in these compartments is extremely low for... 

The available data are insuiScient to determine the pattern or extent of distribution in human tissues after oral exposure to this compound. 

Humans can synthesize 12 of the 20 common amino acids from the amphiboHc intermediates of glycolysis and of the citric acid cycle (Table 28-1). While nutritionally nonessenrial, these 12 amino acids are not nonessential. AH 20 amino acids are biologically essential. Of the 12 nutritionally nonessential amino acids, nine are formed from amphibolic intermediates and three (cysteine, tyrosine and hydroxylysine) from nutritionally essential amino acids. Identification of the twelve amino acids that humans can synthesize rested primarily on data derived from feeding diets in which purified amino acids replaced protein. This chapter considers only the biosynthesis of the twelve amino acids that are synthesized in human tissues, not the other eight that are synthesized by plants. 

Collagen, the major component of most connective tissues, constimtes approximately 25% of the protein of mammals. It provides an extracellular framework for all metazoan animals and exists in virmally every animal tissue. At least 19 distinct types of collagen made up of 30 distinct polypeptide chains (each encoded by a separate gene) have been identified in human tissues. Although several of these are present only in small proportions, they may play important roles in determining the physical properties of specific tissues. In addition, a number of proteins (eg, the Clq component of the complement system, pulmonary surfactant proteins SP-A and SP-D) that are not classified as collagens have... 

Table 48-1 summarizes the types of collagens found in human tissues the nomenclamre used to designate types of collagen and their genes is described in the foomote. 

Osteopetrosis (marble bone disease), characterized by increased bone density, is due to inability to resorb bone. One form occurs along with renal tubular acidosis and cerebral calcification. It is due to mutations in the gene (located on chromosome 8q22) encoding carbonic anhydrase II (CAII), one of four isozymes of carbonic anhydrase present in human tissues. The reaction catalyzed by carbonic anhydrase is shown below ... 

Hydroxylation is the chief reaction involved in phase 1. The responsible enzymes are called monooxygenases or cytochrome P450s the human genome encodes at least 14 families of these enzymes. Estimates of the number of distinct cytochrome P450s in human tissues range from approximately 35 to 60. The reaction catalyzed by a monooxygenase (cytochrome P450) is as follows ... 

Members of at least 11 famihes of cytochrome P450 are found in human tissue. 

Jockers, W. Wretouy, E. Pfleiderer, 6. Quantitation of creatine kinase isoenzymes in human tissues and sera by an immunological method. Clin. Chim. Acta. (1975),... 

Fig. 7.3 Distribution of 8-carotene in human tissues. After Kaplan et al., 1990.

During, A. et al., P-Carotene 15,15-Dioxygenase activity in human tissues and cells evidence of an iron dependency, J. Nutr. Biochem., 12, 640, 2001. 

LeGeros, R. Z. LeGeros, P. (1984). Phosphate minerals in human tissues. In Nriagu, J. O. Moore, P. B. (eds.) Phosphate Minerals, Chapter 12. Berlin Springer-Verlag. 

Measurement of exposure can be made by determining levels of toxic chemicals in human serum or tissue if the chemicals of concern persist in tissue or if the exposure is recent. For most situations, neither of these conditions is met. As a result, most assessments of exposure depend primarily on chemical measurements in environmental media coupled with semi-quantitative assessments of environmental pathways. However, when measurements in human tissue are possible, valuable exposure information can be obtained, subject to the same limitations cited above for environmental measurement methodology. Interpretation of tissue concentration data is dependent on knowledge of the absorption, excretion, metabolism, and tissue specificity characteristics for the chemical under study. The toxic hazard posed by a particular chemical will depend critically upon the concentration achieved at particular target organ sites. This, in turn, depends upon rates of absorption, transport, and metabolic alteration. Metabolic alterations can involve either partial inactivation of toxic material or conversion to chemicals with increased or differing toxic properties. 

A good example of the many successftil DfE Partnerships is the Furniture Flame Retard-ancy Partnerhip. Pentabromodiphenylether (PentaBDE) was the primary flame retardant used in low density, flexible polyurethane furniture foam. Due to concerns over its use and the fact that the chemical was found widespread in the environment and in human tissue and breast milk, PentaBDE was voluntarily phased out of production by US manufacturers in January 2004. The industry needed alternatives in order to meet furniture flame retardancy requirements, but did not have the human and environmental health and safety information needed in order to compare the alternatives. DfE worked with the furniture manufacturers, foam manufacturers, and flame-retardant chemical suppliers along with governmental and environmental groups to evaluate possible alternatives. 

Garter, K.C., Brown, G., Trowbridge, I.S., Woolston, R.-E. and Mason, D.Y. (1983). Transferrin receptors in human tissues their distribution and possible clinical relevance. J. Clin. Pathol. 36, 539-545. 

Exposure Levels in Humans. Although some data on the levels of americium in human tissues exposed to natural background levels (food, water, and air) are available, few measurements have been made on the americium content in human tissues. The principal source of information about occupationally exposed individuals is the U.S. Transuranium and Uranium Registries (USTUR) Tissue Program and database, established to document levels and distribution of uranium and transuranium isotopes in human tissues for occupationally exposed workers (USTUR 1999). Several major database files are available. 

Methods for Determining Biomarkers of Exposure and Effect. Analytical methods with satisfactory sensitivity and precision are available to determine the levels of americium in human tissues and body fluids. However, improved methods are needed to assess the biological effects of americium in tissues. 

Phosphofructokinase (PFK) is a key regulatory enzyme of glycolysis that catalyzes the conversion of fructose-6-phosphate to fructose-1,6-diphosphate. The active PFK enzyme is a homo- or heterotetrameric enzyme with a molecular weight of 340,000. Three types of subunits, muscle type (M), liver type (L), and fibroblast (F) or platelet (P) type, exist in human tissues. Human muscle and liver PFKs consist of homotetramers (M4 and L4), whereas red blood cell PFK consists of five tetramers (M4, M3L, M2L2, ML3, and L4). Each isoform is unique with respect to affinity for the substrate fructose-6-phosphate and ATP and modulation by effectors such as citrate, ATP, cAMP, and fructose-2,6-diphosphate. M-type PFK has greater affinity for fructose-6-phosphate than the other isozymes. AMP and fructose-2,6-diphosphate facilitate fructose-6-phosphate binding mainly of L-type PFK, whereas P-type PFK has intermediate properties. 

The hexose phosphate, fructose-1,6-diphosphate, is split by aldolase into two triose phosphates glyceraldehyde-3-phosphate and dihydroxyacetone phosphate. Aldolase consists of four 40-kDa subunits. Three tissue-specific forms exist in human tissues aldolase A (ubiquitous and very active in the muscle), aldolase B (liver, kidney, and small intestine), and aldolase C (specific to the brain). These three isozymes have nearly the same molecular size but differ in substrate specificity,... 

Gross SB, Pfitzer EA, Yeager DW, et al. 1975. Lead in human tissues. Toxicol Appl Pharmacol 32 638-651. 

For many decades, the standard technique for measuring carotenoids has been high-pressure liquid chromatography (HPLC). This time consuming and expensive chemical method works well for the measurement of carotenoids in serum, but it is difficult to perform in human tissue since it requires biopsies of relatively large tissue volumes. Additionally, serum antioxidant measurements are more indicative of short-term dietary intakes of antioxidants rather than steady-state accumulations in body tissues exposed to external oxidative stress factors such as smoking and UV-light exposure. 

Lindqvist, A., Y. G. He, and S. Andersson. 2005. Cell type-specific expression of beta-carotene 9, 10 -monooxygenase in human tissues. J Histochem Cytochem 53(11) 1403-1412. 

Capiello, M., Guiliani, L., Pacifici, G. M., Distribution of UDP-glucuronosyl transferase and its endogenous substrate uridine 5-diphosphoglucuronic acid in human tissues, Pur. J. Clin. Pharmacol. 1991, 41, 345-350. 

Ho DH, Townsend L, Luna MA et al. Distribution and inhibition of dihydrouracil dehydrogenase activities in human tissues using 5-fluorouracil as a substrate. Anticancer Res 1986 6 781-784. 

Stewart M J, Malek K, Crabb DW. Distribution of messenger RNAs for aldehyde dehydrogenase 1, aldehyde dehydrogenase 2, and aldehyde dehydrogenase 5 in human tissues. J Invest Med 1996 44 42-46. 

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