Cellular tests

If patients have experienced anaphylaxis, the identification of any possible elicitor is important to help avoid further episodes. With skin tests and specific IgE antibodies combined with history, a relevant allergy may be detected. Cellular tests monitoring basophil histamine release or basophil activation may be helpful in some patients who resist diagnosis by standard means [26,31]. 

The detection of reactions mediated by specific IgE to agents triggering anaphylaxis may be achieved by means of serological methods serum-specific IgE, or by means of cellular tests which determine the release of basophil mediators (leukotrienes and histamine) or by means of the analysis of basophil expression markers, a technique known as the basophil activation test (BAT). 

Selection of representative bioassays is crucial for successful application of the pT-scale. Sub-cellular tests such as enzyme assays may not be sufficiently relevant in their indicative power of environmental hazard instead of tests using cells or whole organisms. Future refinements to the pT-scale might be the incorporation of additional genotoxicity or immunotoxicity tests to a test battery to augment its diagnostic power in terms of hazard assessment. 

There are several objectives in studying drug metabolism (Table 1). It is obvious that the chosen specific objective dictates the prerequisites of the cellular test system to be fulfilled to have a relevant outcome. If metabolic clearance is to be deduced from the results, a cellular system with metabolic competence as close to that in vivo... 

Drug or xenobiotic metabolism is the most significant determinant of toxicokinetics that is, the fate of a compound in vivo is heavily dependent on metabolism. Metabolic steps that take place within the cell are also the main determinants of how much of the parent compound or a specific metabolite reaches a target organelle in a cellular test system. As metabolism in the target organ for toxicity may lead both to detoxification and/or metabolic activation it is essential to investigate the metabolic competence and characteristics of any cell line used for toxicity studies. 

The situation is very different with chronic effect testing. The scientific community is split on both what tests should be performed and how test results should be interpreted. While a very rough consensus does appear to be developing recently, much work remains to be done in correlating bacterial and cellular tests to ninety day and lifetime effect testing. 

In another study, 42,000 compounds were screened in three different versions of a farnesoid X receptor (FXR) antagonism assay. AlphaScreen, time resolved fluorescence (TRF), and time resolved FRET (TR-FRET) were used. These identified 104, 23, and 57 actives, respectively. Only 18 compounds were identified by all three methods. Further cellular testing showed that only about 30% of them were functionally active, with AlphaScreen identifying more of the functionally active compounds than the other two methods. This group also found that screening mixtures rather than discrete compounds was more likely to result in both false positives and false negatives. ... 

Undeniably, there are a number of patients with exanthema in whom all investigations, including skin, serological, and cellular tests, fail to detect hypersensitivity to penicillins. In such patients, the pathogenesis of the skin lesions remain mysterious. The possibility that interaction between ampicillin and lymphocytes may under some circumstances promote the formation and release of lymphokines is no more than a working hypothesis. 

Non-immediate reactions to quinolones occur but they are not encountered as often as immediate reactions and in-depth studies are so far few. Some of the more often-seen delayed reactions are fixed drug eruptions and maculopapular exanthemas where a T cell mechanism has been demonstrated. Specific T cell clones were identified from patients with ciprofloxacin-induced maculopapular exanthems and about half of the clones proved cross-reactive with related drugs. Reexposure studies in patients with exanthems revealed that cross-reactivity is in fact lower than this. Cellular tests such as lymphocyte transformation tests were judged to be not very useful. However, the lymphocyte transformation test was said to have confirmed the involvement of T cells when peripheral blood... 

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