Tissue-diffusion cell systems

For assessing the absorption potential of specific drug candidates or conducting studies evaluating correlations between drug structure and transport, in vitro models may provide the best approach. Both the tissue-diffusion cell systems and cultured colon cell lines have proved to be particularly useful. 

Once the oxygen has diffused from the alveoli into pulmonary circulation, it must be carried, or transported, in the blood to cells and tissues that need it. Furthermore, once the carbon dioxide has diffused from the tissues into the systemic circulation, it must be transported to the lungs, where it can be eliminated. This section considers mechanisms by which these gases are transported. 

While Franz-type diffusion cells are commonly used to assess in vitro penetration of compounds across the skin, they have also been used for the assessment of compound permeability across the buccal mucosa [19, 71, 104], In this system, buccal mucosa is sandwiched between two chambers, and compound solution is added to the donor chamber with compound-free buffer in the receptor chamber. The receptor chamber is then periodically sampled to assess the amount of compound that has permeated the tissue over time. 

Enolase is a glycolytic enzyme also known as phosphopyru-vate hydratase. Neuron-specific enolase (NSE) is the form of enolase found in neuronal tissue and in the cells of the diffuse neuroendocrine system and the amine precursor uptake, and decarboxylation (APUD) tissue. NSE is found in tumors associated with the neuroendocrine origin, including small cell lung cancer (SCLC), neuroblastoma, pheochromocytoma, carcinoid, medullary carcinoma of the thyroid, melanoma, and pancreatic endocrine tumors. 

Neuroendocrine cells occur in many organs and tissues in the body and are part of the diffuse neuroendocrine system, as described by Pearse and the dispersed neuroendocrine system, described by Gould and DeLellis. Not surprisingly, neuroendocrine cells and neoplasms formed by cells exhibiting neuroendocrine differentiation show similar immunohistochemical features. They contain a variety of biogenic amines, peptide hormones, and neurotransmitters that can be identified biochemically or immunohistochemically. Immunohistochemical markers are useful in showing neuroendocrine differentiation by a neoplasm but are not usually specific. The antibodies commonly employed in demonstrating neuroendocrine differentiation are shown in Table 12.10. 

Determination of the effects of changes in blood flow through the various regions of the cutaneous microvasculature is obviously not possible using traditional Franz-type isolated membrane diffusion cell studies. The ultimate goal of experimental systems is usually to allow quantitative prediction of the absorption and distribution of topically applied solutes that wfll be applicable to the in vivo situation. Therefore, we can deduce that studies examining the effects of changes in cutaneous blood flow are limited to experimental models in which the microvasculature has been preserved and can be effectively perfused and manipulated. Models reported in the htraature to date include isolated perfused tissue models, anesthetized animal studies, and more recently human and animal cutaneous microdialysis studies. 

Martinez, A., Lopez, ]. Sesma, P. (1993). Development of the diffuse endocrine system in the chicken proventriculus. Cell Tissue Res., 271, 107-13. 

The amounts of penetrated substance found in the receptor fluid are considered to be sys-temicaUy available. The epidermis (except for the stratum comeum) and dermis are considered as a sink, therefore the amounts found in these tissues are equally considered as absorbed and are added to those found in the receptor fluid. The amounts that are retained by the stratum comeum at the time of sampling are not considered to be dermally absorbed and, thus, they do not contribute to the systemic dose. The absorption rate and mass balance should be calculated separately for each diffusion cell. Only then, the mean SD can be calculated. 

In systems comprised of cells in culture, there is no formal architecture (such as might be encountered in a whole tissue) that would hinder free diffusion. Such... 

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