Cell culture models, evaluating sensitizing

Cell Culture Models for Evaluation of Sensitizing Potential... 

Cell Culture Models lor Evaluating the Sensitizing Potential ol Xenobiotics... 

One example of a miniaturized LC/MS strategy is the use of 96-well sample plates (Kaye et al., 1996) for extraction. This sample extraction procedure combines batch sample processing within a miniaturized format. Increased sensitivity and decreased volume advances have fostered a new wave of scale-down models. Experiments that were formerly performed at the bench are, instead, performed at the microliter scale in the batch mode. For example, synthetic process research was traditionally performed manually with apparatus at the milliliter level. This approach involves the testing of a range of synthetic conditions for optimum yield and minimum impurity production. Now, process research conditions are tested in microliter levels to produce information on purity and structure (Rourick et al., 1996). This strategy requires fewer reagents and accelerates the evaluation of a wider range of conditions in a shorter time. Another example includes the direct analysis of samples from cell culture experiments (Kerns et al., 1997). 

Drug sensitivity testing for P. vivax and P. ovale remains a problem as continuous culure of these species is difficult due to nutritional and host cell requirements only short term cultures have been used in drug tests [27]. In vitro culture of the exoerythrocytic liver stages of malaria infection have been achieved using hepatocytes and hepatomas to culture P. berghei, P. vivax and P. falciparum [28] but these models have not been used widely in drug evaluation studies. 

We have recently started to analyze the cellular effects of palytoxin in primary cultures of murine neurons. Primary cultures of cerebellar granule cells constitute one of the most reliable, well-characterized, and highly sensitive models for the study of neuronal function and pathology as weU as the effects of poisonous agents." " In this system, we found that palytoxin caused a dose-dependent membrane depolarization as evaluated with the voltage-sensitive membrane probe bis(oxonol) (Figure 31.1). Signihcative differences between control and palytoxin-treated cells were found at toxin concentrations of 5 nM. 

---