Viability parameters

Olinga P, Groen K, Hof IH, De Kanter R, Koster HJ, Leeman WR, Rutten AA, Van Twillert K, Groothuis GM (1997) Comparison of five incubation systems for rat liver slices using functional and viability parameters. J Pharmacol Toxicol Methods 38(2) 59-69... 

The metaUic products released from the prosthesis because of wear, corrosion, and fretting may impair organs and local tissues. In vitro studies have indicated that particulate Co is toxic to human osteoblast-hke cell lines and inhibits synthesis of type-I collagen, osteocalcin and alkaline phosphatase in the culture medium. However, particulate Cr and CoCr alloy are well tolerated by cell lines with no significant toxicity. The toxicity of metal extracts in vitro have indicated that Co and Ni extracts at 50% concentration appear to be highly toxic since aU viability parameters were altered after 24 h. However, Cr extract seems to be less toxic than Ni and Co [Granchi et al, 1996]. 

The biological impact of starch capped copper nanoparticles on mouse embryonic fibroblast (3T3L1) cells in vitro) was also evaluated by various parameters. More than 85 % of the 3T3Llcells were found to be viable, even after 20 hours time exposure which implies minimum impact on cell viability and morphology. The study demonstrates dose dependent cytotoxic potential of SCuNPs, that is non cytotoxic in the nanogram dose and moderately cytotoxic in the microgram doses (Fig. 10). Comparison of SCuNPs with Cu ions and uncapped copper nanoparticles (UCuNPs) revealed that, ions are more cytotoxic than SCuNPs. This observation supports the theory of slow release of ions from starch coated nanoparticles. 

Step (6) can be broken down as given in Table 2.7. If the hardware and its operation is under control, and some experience with similar problems is available, experiments need only be carried out late in the selection process to prove/disprove the viability of a tentative protocol. Laboratory work will earnestly begin with the optimization of instrumental parameters, and will continue with validation. In following such a simulation procedure, days and weeks of costly lab work can be replaced by hours or days of desk work. 

Depending on the scale of production, an important parameter determining the economic viability of poly(3HB) production (besides overall yield and poly(3HB) content) is productivity. Productivities of poly(3HB) production at-... 

Parametric uncertainty A great number of bacterial species carry out the transformations of organic load and nutrients in wastewater treatment processes without direct or easily comprehensible relationships between the microbial populations and viability. The role of each bacterial species is fuzzy [30], and aspects such as cellular physiology and its modeling are not easily understood from external measurements [18], [68]. As a first consequence, the kinetics of these transformations is often poorly or inadequately known [66]. Extensive efforts to model the kinetics have been undertaken, but these have not been successful to elucidate how yield coefficients, kinetic parameters and the bacterial population distribution change as a function of both, the influent composition and the operating conditions. 

The viability and function tests described above are used to evaluate the hepatocytes within the slice. Up to now, tests to measure the viability of the non-parenchymal cells have not been reported. The presence of the latter cell types is one of the conceptual advantages of slices as compared to isolated hepatocytes. As some drug targeting devices are designed to target non-parenchymal cells in the liver, the development of tests for the sinusoidal cell types deserves more attention. For example, the uptake of substrates such as succinylated human serum albumin (Suc-HSA,which is specifically endocytosed by endothelial cells [79]), or hyaluronic acid [80], can be used to assess the functionality of endocytotic pathways in the endothelial cells in the liver [81]. Other modified proteins that are specifically taken up by Kupffer cells such as mannosylated HSA, may be used to assess the functionality of the endocytotic pathway in Kupffer cells [79]. Another parameter which can be used to assess the functionality of these non-parenchymal liver cells, is the excretion of cytokines in response to pro-inflammatory stimuli. Non-parench5mal cell function in liver slices will be described in more detail in the Section 12.7. 

Fig. 3. Schematic of teratogenicity screening assay. Fertilized eggs are collected within a few hours of spawning. The chorions can be removed by gentle enzymatic treatment with manual removal as needed. The embryos are then cultured for the desired period of time. When embryos are incubated in 1 ml of medium, continuous exposure (without medium changes) is possible for at least 5 days. Embryos are exposed to the test substance in the culture medium. At the desired timepoint(s) (e.g., 5 dpt), larvae can be evaluated for viability and developmental parameters. (Reprinted from Brannen et al. (4), by permission of John Wiley and Sons.).

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