Animals, differential tissue analysis

Because PB-PK models are based on physiological and anatomical measurements and all mammals are inherently similar, they provide a rational basis for relating data obtained from animals to humans. Estimates of predicted disposition patterns for test substances in humans may be obtained by adjusting biochemical parameters in models validated for animals adjustments are based on experimental results of animal and human in vitro tests and by substituting appropriate human tissue sizes and blood flows. Development of these models requires special software capable of simultaneously solving multiple (often very complex) differential equations, some of which were mentioned in this chapter. Several detailed descriptions of data analysis have been reported. 

Structure-activity relationships are generally applied in the pharmaceutical sciences to drug molecules. The value of any structure-activity correlation is determined by the precision of the biological data. So it is with studies of the interaction of nonionic surfactants and biomembranes. Analysis of results is complicated by the difficulty in obtaining data in which one can discern small differences in the activity of closely related compounds, due to i) biological variability in tissues and animals, ii) potential differential metabolism of the surfactants in a homologous series (2), iii) kinetic and dynamic factors such as different rates of absorption of members of the surfactant homologous series (2) and iv) the typically biphasic concentration dependency of nonionic surfactant action (3 ). 

The conditions under which the drug is used need to be estimated as do acceptable residues linked to the level of acceptable risk to the consumer. The acceptable level of risk, which is determined in theory at the risk management stage, has already been expressed in terms of residues by the ADI under hazard characterization. Moreover, the elements considered for hazard identification, hazard characterization, and exposure assessment make it possible, for a given form of utilization of a particular substance, to establish a profile of residues in animal tissues and to associate this with a profile of consumer exposure. Comparison of this consumer profile and ADI indicates whether the mode of utilization of the substance is acceptable or not. Analysis of the different results of residue content in animal products then provides an indication of level of residues in one or several animal tissues, making it possible to differentiate between veterinary drug applications that do or do not permit compliance with the ADI. 

Toxicokinetics studies are designed to measure the amount and rate of the absorption, distribution, metabolism, and excretion of a xenobiotic. These data are used to construct predictive mathematical models so that the distribution and excretion of other doses can be simulated. Such studies are carried out using radiolabeled compounds to facilitate measurement and total recovery of the administered dose. This can be done entirely in vivo by measuring levels in blood, expired air, feces, and urine these procedures can be done relatively noninvasively and continuously in the same animal. Tissue levels can be measured by sequential killing and analysis of organ levels. It is important to measure not only the compound administered but also its metabolites, because simple radioactivity counting does not differentiate among them. 

As with the animal monomeric and heterotrimeric G-proteins, the proteins identified appeared to show differential expression within the plant tissues. Northern blot analysis showed that transcripts encoding GPAl were most abundant in vegetative tissue and least abundant in floral and apical meristems [89], whilst immunogold staining supported this and also showed that GPAl was strongly expressed in vascular tissue [153]. 

After sampling, the sample is prepared for analysis. Usually, each different type of sample material requires specially adapted sample preparation, extracting the vitamins from the matrix. This is often combined with a preliminary concentration and purification step. Roughly three application fields can be differentiated that pose different demands determination of vitamin content in samples from human subjects and animals, e.g., plasma and tissue determination of vitamin content in feed, food, plants, processed plants, plant products, and microorganisms and determination of added vitamin content in fortified products, e.g., tablets, feed, or food. 

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