Human tissue, lead levels

Numerous observations of non-linear relationships between PbB concentration and lead intake in humans provide further support for the existence of a saturable absorption mechanism or some other capacity limited process in the distribution of lead in humans (Pocock et al. 1983 Sherlock et al. 1984, 1986). However, in immature swine that received oral doses of lead in soil, lead dose-blood lead relationships were non-linear whereas, dose-tissue lead relationships for bone, kidney and liver were linear. The same pattern (nonlinearity for PbB and linearity for tissues) was observed in swine administered lead acetate intravenously (Casteel et al. 1997). These results suggest that the non-linearity in the lead dose-PbB relationship may derive from an effect of lead dose on some aspect of the biokinetics of lead other than absorption. Evidence from mechanistic studies for capacity-limited processes at the level of the intestinal epithelium is compelling, which would suggest that the intake-uptake relationship for lead is likely to be non-linear these studies are discussed in greater detail in Section 2.4.1. 

Therapeutic applications of antibody-toxin conjugates may be limited because (1) antibody-toxin conjugates distribute nonspecifically to organs such as the liver and cause severe toxicity, (2) the bacterial toxin is immunogenic to humans, (3) tumor-associated antigens are often found in normal tissue (although levels are low), and (4) premature release of toxin from the antibody conjugate leads to systemic toxicity. 

In practice there is little evidence for the migration of PCBs from packaging (JFSSG, 1999a). There is considerably more evidence for the other two routes leading to PCBs in food. Indeed, historical trends can be drawn up for residues of PCBs in human fat, breast milk and fish. There has been a very gradual decline in levels of these organochlorine compounds in the environment, food and human tissues. This is entirely consistent with the persistence of these compounds. 

A striking aspect of lead in the body is its very rapid transport to bone and storage there. Lead tends to undergo bioaccumulation in bone throughout life, and about 90% of the body burden of lead is in bone after long-term exposure. The half-life of lead in human bones is estimated to be around 20 years. Some workers exposed to lead in an industrial setting have as much as 500 mg of lead in their bones. Of the soft tissues, the liver and kidney tend to have somewhat elevated lead levels. 

The major aldehyde products of lipid peroxidation are malon-dialdehyde and 4-hydroxynonenal (Table 1, Fig. 4). Malondi-aldehyde can react with DNA to generate adducts at the bases A, C, and G. The mutagenic adduct MIG (pyrimido(l,2-a)purin-10(3H)one) has been detected at levels as high as 1 adduct per 10 nucleosides in human tissues. MIG is a reactive electrophile that can undergo further modification, leading to crosslinking of an adducted DNA strand to the opposite strand, or to some protein (22). Exocyclic etheno adducts can also arise from lipid peroxidation, possibly by reaction of an epoxide of 4-hydroxynonenal with A, C, or G in DNA. 

Kallikrein is a proteinase enzyme, which converts kininogen to vasodilative kinin peptides. The human tissue kallikrein gene, in the form of naked pDNA (CMV-cHK), was directly delivered by intracerebroventricular injection into hypertensive rats. The expression of human tissue kallikrein protein was identified in the cortex, cerebellum, brain stem, hippocampus, and hypothalamus of the treated rats. The expression level and its effect could lead to understanding the role of vasodilative KKS on the pathogenesis of hypertension. 

When assessing the levels of Cu,Zn-SOD in tissues, one must be aware that the enzyme is released from erythrocytes by hemolysis. Particular attention must be paid to this problem when Cu,Zn-SOD is measured in human serum. Human erythrocytes contain approximately 0.5-0.75 pg Cu,Zn-SOD per gram of hemoglobin. Even trace hemolysis can therefore lead to misinterpretation. Because many of the previous studies on tissue and serum Cu,Zn-SOD did not take into account the contribution from hemolysis, many of the data so far reported should be reinvestigated. Hartz and Deutsch carefully determined the content of Cu,Zn-SOD in various human tissues using a single radial immunodiffusion technique... 

An optimum level of main and trace elements is required for a number of metabolic and physiological processes in the human body since both deficiency and excess may lead to different metabolic disorders. However, there is a paucity of reliable data regarding elements in human tissues. This is especially true concerning normal aged human brains and the brains of AD patients. 

The levels of lead and the distribution of lead in normal adult human tissues are shown in Table 1 (B9, K3, T2, T3). Certain tissues, notably the aorta and liver, and especially the adrenal and thyroid glands and the jejunum portion of the small intestine, appear to contain higher portions of lead than others. Kehoe et al. (K3) have shown the accumulation of lead in the bones. Sognnaes (S5) has shown that lead in the bulk enamel of teeth is 30 ppm in young teeth to 90 ppm in old teeth. Up to 500 ppm is reported in the peripheral enamel. 

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