Tissue measurements

The uptake of TRA into cervical tissue was determined by measuring tissue radioactivity following insertion of the collagen sponge cervical cap containing tritium-labeled TRA. The TRA concentrations peaked at 4 hr and then diminished rapidly by 24 hr. Since measurements of blood samples revealed that no systemic absorption had occurred, high local concentrations over an extended period of time may be possible without systemic side effects. 

The study of diisopropyl methylphosphonate distribution in a lactating Jersey cow was the only study that used multiple doses of diisopropyl methylphosphonate (Ivie 1980). In this single cow, radioactivity was detected in the blood 2 hours after dosing with [14C]-radiolabeled compound but not in the tissues. The animal had received diisopropyl methylphosphonate in one gelatin capsule for 5 days before the radiolabeled dose was administered. If tissue uptake in the cow was similar to that in dogs, measurements made 2 hours after dosing may not have provided an opportunity to measure tissue uptake of label. After 24 hours, 0.1% of the administered label was found in the cow s milk (Ivie 1980). 

Measurable levels of endrin have not been found in adipose tissue of the general population (Stanley 1986 Williams et al. 1984). Measurable tissue concentrations of endrin have been observed in cases of acute poisoning. The time of sample collection is critical as endrin residues in tissues decline rapidly after exposure has ceased. 

Volumes and flows are based on actual measured tissue volumes and blood flows to various organs, which have been tabulated for many species [5]. The basic approach for the development of a PBPK model, including model formulation, parameterization and validation, was described in detail by Clewell et al. [1]. These authors also included discussions on technical topics ranging from numerical solutions of PBPK models to sensitivity analysis. 

C.Y. Shiue, A.P. Wolf, M. Friedkin, Synthesis of 5 -deo -5- F-fluorouridine and related compounds as probe for measuring tissue proliferation in vivo, J. Label. Compds Radiopharm. 21 (1984) 865-873. 

The gray (Gy) is the SI unit for measuring the amount of energy absorbed per kilogram of tissue exposed to a radiation source 1 Gy = 1 J/kg. The rad (radiation absorbed dose) also measures tissue exposure and is more often used in medicine. 

Relatively great assimilation efficiencies, in addition to the measured tissue distribution of PFAs in fish, are supportive of the idea that enterohepatic recirculation may be an important factor limiting PFA depuration. The greatest concentrations of PFAs in tissues are measured in the blood > kidney > liver > gall bladder [68]. The tissue distribution of fish corresponds well with the observed tissue distribution in eagles (Table 16). Evidence of enterohepatic recirculation in rats has been demonstrated to affect the rate of elimination for PFAs [71]. 

Bruulsema JT, Hayward JE, Farrell TJ, Patterson MS, Heinemann L, Berger M, Koschinsky T, Sandahl-Christiansen J, Orskov H. Correlation between blood glucose concentration in diabetics and noninvasively measured tissue optical scattering coefficient. Optics Letters 1997, 22, 190-192. 

A physiologically based pharmacokinetics (PBPK) model based on the ventilation rate, cardiac output, tissue blood flow rates, and volumes as well as measured tissue/air and blood/air partition coefficients has been developed (Medinsky et al. 1989a Travis et al. 1990). Experimentally determined data and model simulations indicated that during and after 6 hours of inhalation exposure to benzene, mice metabolized benzene more efficiently than rats (Medinsky et al. 1989a). After oral exposure, mice and rats appeared to metabolize benzene similarly up to oral doses of 50 mg/kg, above which rats metabolized more benzene than did mice on a per kg body weight basis (Medinsky et al. 1989b). This model may be able to predict the human response based on animal data. Benzene metabolism followed Michaelis-Menton kinetics in vivo primarily in the liver, and to a lesser extent in the bone marrow. Additional information on PBPK modeling is presented in Section 2.3.5. 

Tissue residues alone do not convey information about biological responses to chemical exposure. Furthermore, measuring tissue residues is not feasible with chemicals that do not readily bioaccumulate, or with complex mixtures that require time and cost-intensive analyses that may not identify all toxic chemicals. In such cases, other indirect measures may be preferable for indicating a biological response to a toxicologically significant exposure (i.e., a biomarker, see below). 

It has been claimed by some workers that Li is more readily transported into erythrocytes than is Li and that there are differences in their biological effects (72). It has also been postulated that Li may produce fewer side effects or less toxicity than the naturally occurring isotope mixture (73). Li nuclear magnetic resonance (NMR) spectroscopy in vivo has been used to measure tissue lithium levels in humans noninvasively and with safety. These experiments showed tissue lithium concentrations significantly lower than those in the serum (74). The NMR technique has been used also to distinguish the isotopes in transport studies in red blood cells (75, 76) and in other cell types (77). 

Chemical composition is an important contributor to bone quality, a term that encompasses the effects of architecture, composition and remodeling dynamics. An important advantage of infrared (IR) and Raman imaging in bone studies is that they allow the imaging of parameters that measure tissue quality and competence. These are usually measured as band height or band area ratios, and in some cases as band widths. Although measures of tissue properties are similar in both IR and Raman spectroscopy, the IR metrics have been validated with other techniques. 

C22. Connelly, C. M., Methods for measuring tissue oxygen tension theory and evaluation the oxygen electrode. Federation Proc. 16, 681-684 (1957). 

Without doubt vitamin E is the most important lipid-soluble chain-breaking antioxidant in the human body. It is able to interact with lipid peroxyl radicals and is also able to react with singlet oxygen. The role of vitamin E as an antioxidant in vivo has been established several times by measuring tissue lipid peroxidation in vitamin E-deficient or in vitamin E-supplemented animals. 

In the future, tissue concentrations as well as blood concentrations may be measured. For example, while most centers currently measure cyclosporine concentrations to estimate the potential for immunosuppressive effects, it may be advantageous to monitor IL-2 concentrations. One of the primary actions of cyclosporine is the inhibition of IL-2 prodnction. Furthermore, perhaps it would be beneficial to measure tissue concentrations of IL-2 in the transplanted organ to get a better estimate of the extent of immunologic suppression. 

Figure 15. Diffuse reflectance distributions used to measure tissue absorption and scattering properties non-invasively. (a,b) principle of the technique, showing light entering a point on the tissue surface and the measured radial distribution of the diffusely reflected (backscattered) light that depends on the tissue absorption and scattering properties, (c) external surface probe (courtesy Dr M. Patterson, Hamilton, Canada), (d) endoscopic probe (courtesy Dr R. Bays and colleagues, Lausanne, Switzerland) in this case the distribution is measured along the probe from light input at the end, with the probe placed flat on the tissue (e.g. esophagus) surface.

Phylogenetically unrelated species Times of measurement Types of measurement Tissue types (green vs. non-photosynthetic)... 

FIGURE 21.5 A schematic diagram of the four-electrode technique for measuring tissue conductivities. Current, I, is passed through the outer two electrodes, and the potential, V, is measured between the inner two. The interelectrode distance is s. 

The analysis of a large number of neurotransmitters and their metabolites as TMS denvatives has been excellently reviewed by Abramson and coworkers (1974). The electron impact (El) spectra of all the TMS-amino acids have also been reviewed (Iwase et al., 1979) In neurochemical studies, a number of workers have used the TMS derivatization procedure to measure tissue GABA (Cattabeni et al., 1976, 1977 Holdiness et al., 1981 Haseyawa et al, 1981). TMS-glutamate has been found to be extremely valuable for GC-MS analysis in the Cl mode with ammonia as the reagent gas (Dessort et al, 1982). An example of the use of TMS derivatives to monitor glutamate and aspartate release in brain dialysis experiments is presented in Fig. 4. 

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