In vitro assay system

Identification of proteins that bind to Z-DNA added one further step to the establishment of the presence of Z-DNA in vivo and its possible biological role. Herbert and Rich [22] demonstrated an in vitro assay system where one type of double-stranded RNA adenosine deaminase, called DRAD-binding Z-DNA. There are evidences that topoisomerase II from Drosophila, hiunan and calf thymus recognizes a number of DNA shapes, including Z-DNA [34,35]. Bloomfield and coworkers [36] have found that the condensation of plasmids is enhanced by Z-DNA conformation in d(CG)n repeats. The information related to B-Z transition [31], the effect of ligands on it [28,29] and X-ray crystal structure data [37,38] appear to suggest that the possible biological role of this polymorphic form of DNA will be soon established. 

Dibromoethane tested positive for mutagenicity with or without metabolic activation in fungi and mammalian cell lines in in vitro assay systems (Brimer et al. 1982 Clive et al. 1979 ... 

Many in vitro assay systems have been developed for studying substances which interact with the 5-HT3 receptor. Outlined in the next section are those most commonly used to assess 5-HT3 receptor antagonist activity. This is followed by a section on the in vivo tests to assess 5-HT3 receptor activity,... 

If bile acids do have carcinogenic effects in vivo, one would expect these compounds to display certain genotoxic and carcinogenic effects utilising established in-vitro assay systems. 

Apostolidis S, Chandra T, Demirhan I, Cinatl J, Doerr HW, Chandra A (2002) Evaluation of carcinogenic potential of two nitro-musk derivatives, musk xylene and musk tibetene in a host-mediated in vivo/in vitro assay system. Anticancer Res 22 2657-2662... 

The WHO/IPCS international workshop on skin sensitization in chemical risk assessment (WHO/IPCS 2007) concluded No in vitro assay systems for identification of skin sensitizing... 

There was no evidence of genotoxcity in a number of in vitro assay systems. ... 

Cai G, Lian J, Shapiro SS et al (2000) Evaluation of endothelial cell migration with a novel in vitro assay system. Methods Cell Sci 22 107-114... 

This work is also notable in that Cole et al. performed detailed aggregation studies of the heme MPPIX using UV-vis and fluorescence spectroscopies to detect the formation of 71-71 hetero-metalloporphyrin assemblies under assay conditions. By employing UV-vis absorbance spectroscopy, the aggregation of porphyrin and metalloporphyrin systems may be examined. The in vitro assay system used for hemozoin... 

Ashby J, de Serres FJ, Draper M, et al. 1985. Overview and conclusions of the IPCS collaborative study on in vitro assay systems. Progress in Mutation Research 5 117-174. 

In Vitro Assay System to Monitor Tumor-Specific Cytotoxicity. 175... 

Further, eleven 4-phenyl-3,5-diacetyl-1,4-DHPs substituted at the C-4 phenyl ring were synthesized and compared for their cytotoxic activity and MDR reversing activity in in vitro assay systems. Among them, compound G7 (68) showed the highest cytotoxic activity against human promyelocytic leukemia HL-60 and human squamous cell carcinoma HSC-2 cells. However, no compounds tested produced radicals at pH 7.4-12.5. The activity of Pgp... 

Gordon VC (1992) Utilization of biomacromolecular in vitro assay systems in the prediction of in vivo toxic... 

For example, the induction of metabolizing enzymes by a chemical can greatly modify its PK and that of other substances, which is the subject of metabolic interactions [59], Intestinal barrier alterations due to intestinal toxicity can also affect PK [3]. Toxicity-induced retro-action mechanisms can also increase volumes of distribution The interaction of a chemical with aromatase can lead to a decrease in estradiol production and hence a decrease in FSH secretion, followed by a decrease in follicular growth and a reduction of the ovary volume [56], This should have implications for the design of in vitro assay systems. Integrated systems, such as those coupling metabolism and effect observations in human on chip micro-devices [5], offer a way to model experimentally the PK/PD continuum. 

Wienkers, L. C. and Heath, H. G. (2005) Risk assessment for drug-drug interactions caused by metabolism-based inhibition of CYP3A4 using automated in vitro assay systems and its application in early discovery process. Drug Metab. Dispos. 35 (7), 1232-1238. 

Nab assays determine the potential to neutralize in vivo. However, these in vitro assay systems are static systems that do not take into consideration the dynamic interactions that occur in vivo (e.g., clearance of ADA-dmg immune complexes, equilibrium/affinity between drug/antibody/target). There are examples of Nab (even to endogenous protein) that have no/minimal impact on drug efficacy, pharmacodynamics, or adverse events [24,25], Thus, one shouldkeep in mind that whenNab assays are used, the results must be evaluated in the context of other clinical end points to determine their significance. 

In vitro assay systems can also be used to show that ACAT uses oleoyl-CoA and palmitoyl-CoA preferentially as substrates [15,16,22]. This specificity is in good agreement with the fatty acid composition typically found upon analysis of tissue CE. However, some tissues, such as the rat adrenal, ovary, and testis, are rich in polyunsaturated fatty acids, raising the possibility that these tissues may contain an ACAT enzyme with a different fatty acid specificity [23]. 

Inhibition of cholesterol biosynthesis constitutes an important strategy to the lowering of higher blood total and LDL cholesterol levels. Several in vitro assay systems have been used as screening methods for developing novel leads for cholesterol biosynthesis inhibitors. 

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