Tissue retention

The bioavailability of an element in the diet is determined as the fraction of element that has been absorbed in the intestine, retained by the body, and utilized for physiological function, including deposition into storage tissues [18]. The actual element utilization of an administered label, however, is difficult to measure directly. Major functional or storage compartments, such as liver, muscle tissue, and bone, are difficult to access. They require tissue biopsies, which can be taken with minimal associated health risks, but can hardly be considered a routine sampling approach for research purposes in healthy volunteers. The only exception is iron, for which two-thirds of body iron circulates as hemoglobin in blood, which can be easily sampled. This has led to the development of two different approaches to assess iron absorption and bioavailability in the human body. 

The first approach is based on the early work of Dubach et al. [38], who used radiotracers to determine iron bioavailability. In healthy individuals it takes about 14 days until freshly absorbed iron is incorporated into reticulocytes, that is, freshly matured red blood cells. The amount ratio of stable isotopic label to natural iron, that is, the tracer to tracee ratio, can be determined using IDMS concepts in a 

The above approach is based on estimates of blood volume and efficiency of erythrocyte incorporation of the isotopic label, unless it is determined directly in the studied subject. These potential sources of bias cancel out for relative measurements to compare iron absorption from one test meal against another in the same individual. This is possible by using two different isotopes, such as Fe and Fe, to label meals differently, which are then fed on two consecutive days [9,44]. 

Such an approach is often used to identify the effect of a specific food component on iron absorption or to compare iron absorption from two different food fortification compounds. 

In certain situations, absolute information on iron absorption is required. 

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Reports of lead-nutrient interactions in experimental animals have generally described such relationships in terms of a single nutrient, using relative absorption or tissue retention in the animal to index the effect. Most of the data are concerned with the impact of dietary levels of calcium, iron, phosphorus, and vitamin D. These interaction studies are summarized in Table 2-12. 

Zinc Rat Tissue retention Low zinc diet enhances brain lead levels Bushnell and Levin 1983... 

Sawada and coworkers [25-27] studied the iso-pH 7.4 MDCK permeabilities of very lipophilic molecules, including chlorpromazine (CPZ) [25], These authors included 3% wt/vol bovine serum albumin (BSA) on the apical (donor) side, and 0.1-3% BSA on the basolateral (acceptor) side, and found that plasma protein binding greatly affected the ability of molecules to permeate cellular barriers. They observed cell tissue retention of CPZ ranging from 65 to 85%, depending on the... 

Although absorption of fluorocarbons via inhalation is rapid, and maximal blood concentrations are reached in about 15 min, pulmonary uptake is low (Azar et al. 1973 Trochimowicz et al. 1974 Mullin et al. 1979). Negligible metabolism and tissue retention take place. Blood concentrations fall rapidly following cessation of exposure as the parent compound is exhaled unchanged. Rapid elimination is typical of poorly soluble materials with high vapor pressures and demonstrates a lack of potential to bioaccumulate (Emmen et al. 2000). 

Ethylbenzene is rapidly absorbed after inhalation exposure of humans, as shown by the excretion of ethylbenzene metabolites and tissue retention of ethylbenzene in exposed workers and volunteers (Engstrom Bjurstrom, 1978 Engstrom, 1984a Dmmmond et al, 1989). There occurs rapid absorption upon dermal application of... 

Long-term tissue retention of the excipient or a metabolite of the excipient, resulting in local tissue reaction or other pathophysiological responses that are suggestive... 

Many athletes who have used high aromatizing AAS have reported a delayed period of HPTA regeneration. As such post-cycle lean mass tissue retention suffers as a negative reaction to suppressed endogenous androgen production. If the boy s are shrunken so is the athlete they are attached to. 

There is also the drug synergy that results from a T-4, T-3, T-2 stack to consider for overall effectiveness and reduced dosage requirements. Some athletes have reported an improved rate of fat loss and better lean tissue retention with this technique. 

Greger JL, Chang MM, Radanowski GN. 1995. Comparison of tissue retention of aluminum and Ga-67 Effects of iron status in rats. Toxicology 100 1-9. 

Jouhanneau P, Raisbeck GM, Yiou F, et al. 1997. Gastrointestinal absorption, tissue retention, and urinary excretion of dietary aluminum in rats determined by using 26A1. Clin Chem 43 1023-1028. 

Despite several decades of clinical experience and animal study, the pathophysiology of brain encephalopathy is far from understood. One of the main reasons for the complexity of the research on Al is the difficult interaction with molecules found in biological systems. In most natural systems, a small fraction of Al is found as the simple Al3+ aquo ion. Thus Al absorption, excretion, tissue retention, and deposition will all depend on the properties of the Al3+ complexes formed with biological ligands. Unfortunately, the search for an accurate description of Al complexation equilibria and kinetics has been consistently frustrated by the tendency of both free Al3+ ion and simple Al complexes to hydrolyze at or below neutral pH. 

The U.S./Canadian tolerable upper level is set at 1,000 mg per day, based on reports of prolonged prothrombin time in people receiving anticoagulants and consuming 1,100 to 2,100 mg of vitamin E per day. It is noteworthy that although the report specifically excluded the 2S isomers of synthetic a-tocopherol from calculations of nutritional requirements, this tolerable upper level includes all forms of the vitamin, regardless of their tissue retention and biological activity (Institute of Medicine, 2000). 

Experimental animals that have been exposed to ititrous oxide to deplete vitamin B12 show an increase in the proportion of liver folate present as methyl-tetrahydrofolate (85% rather than the normal 45%), largely at the expense of unsubstituted tetrahydrofolate and increased urinary loss of methyl-tetrahydrofolate (Horne et al., 1989). Tissue retention of folate is impaired because methyl-tetrahydrofolate is a poor substrate for polyglutamyl-folate synthetase, compared with unsubstituted tetrahydrofolate (Section 10.2.2.1). As a result of this, vitamin B12 deficiency is frequently accompanied by biochemical evidence of functional folate deficiency, including impaired metabolism of histidine (excretion of formiminoglutamate Section 10.3.1.2) and impaired thymidylate synthetase activity (as shown by abnormally low dUMP suppression Section 10.3.3.3), although plasma concentrations of methyl-tetrahydrofolate are normal or elevated. 

Salbe, A. D., and Lovander, O. A. (1990). Comparative toxicitj and tissue retention of selenium in methionine-deficient rats fed sodium selenate or i.-selenomethi nine. /-Nutr. 120,207-212. 

Long-term tissue retention of parent compound or metabolite(s) resulting in local tissue reactions or other pathological responses... 

Auranofin is a triethylphosphine gold derivative for oral administration. It is in some respects strikingly different from the rest. Some 25% of an oral dose is absorbed through the intestinal wall and blood concentrations are some 15-25% of those reached with parenteral therapy. Auranofin is bound to cellular elements of the blood, is excreted mainly in the feces, and exhibits less tissue retention and total body gold accumulation than parenteral forms. It is more effective in acute inflammatory models and is a potent inhibitor of lysosomal enzyme release, antibody-dependent cellular toxicity, and superoxide production. Auranofin also affects humoral and cellular immune reactions. However, some have found auranofin to be rather less effective than parenteral gold. Auranofin is used in doses of 2-9 mg/day (generally 6 mg/day), which is less than the dose originally recommended. 

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