In vitro model

Clark RD et al. (2004) Modelling in vitro hepatotoxicity using molecular interaction fields and SIMCA. J Mol Graph Model 22(6) 487-497... 

Kramer, S. D. Hurley, J. A. Abbott, N. J. Begley, D. J., Lipids in blood-brain barrier models in vitro I TLC and HPLC for the analysis of hpid classes and long polyunsaturated... 

These findings were confirmed and extended by in vitro electrophysiological studies of slices from normal animals that revealed that subtle (e.g. 20%) reductions of inhibitory synaptic function could lead to epileptiform activity. Importantly, activation of excitatory synapses is often pivotal in the expression of a seizure in distinct models in vitro. In addition to these important pharmacological observations, electrophysiological analyses of individual neurons during a partial seizure revealed that neurons undergo a massive depolarization and fire action potentials at high frequencies (Fig. 37-1) [3], This pattern of... 

Taken together, HDACis are promising candidates for harnessing neuronal loss, both in apoptotic models in vitro, and in several models of neurodegenerescence in vivo. However, they are not the wonder drug and improvement in different ways need to be performed. 

More complex, second order interactions may be imagined, involving more than one natural enemy. For example, consider insects to which tannins are important deterrents and digestion inhibitors. As mentioned above, elevated gut pH appears to be a way of dealing with tannins, since tannin-protein complexes are dissociated or inhibited at alkaline pH (16,32). Indeed, using a model in vitro system in which hemoglobin is employed as a protein substrate, we found that several natural tannins and phenolic extracts do not precipitate this protein when the pH exceeds about... 

Method Genomics, traditional biomedical research Animal models, in vitro assays Rational drug design, high throughput screening, combinatorial chemistry Medicinal chemistry In vivo assays, animal models I N D Healthy human volunteers Patients N Patients D A... 

A14. Alexander, E., Buyon, I. P., Provost, T. T., and Guamieri, T., Anti-Ro/SS-A antibodies in the pathophysiology of congenital heart block in neonatal lupus syndrome, an experimental model. In vitro evectrophysiologic and immunocytochemical studies. Arthritis Rheum. 35, 176—189 (1992). 

In addition to whole animal models, in vitro studies are generally used to complement and specify the data obtained using perfused organs, tissue or cell cultures, and microsomal preparations. The use of these models allows a more detailed or partial study of the effects of PAC and can decrease the ethical concerns, but it has disadvantages as well. For instance, the cells are often not easy to culture and maintain, which in turn results in diluted samples. 

Dee, K. G, Andersen, T. T., Rueger, D. G, and Bizios, R., Conditions which promote mineralization at the bone/implant interface a model in vitro study. Biomaterials 17, 209-215... 

It is also worthy of mention that a gamma distribution function proposed by Djordjevic [118] for modeling in vitro dissolution profiles implies a relevant type of time dependency for the amount of drug dissolved. 

Djordjevic, A. and Mendas, I., Method for modelling in vitro dissolution profiles of drugs using gamma distribution, European Journal of Pharmaceutics and Biopharmaceutics, Vol. 44, No. 2, 1997, pp. 215-217. 

Flurbiprofen is a cyclooxygenase (COX)-inhibiting non-steroidal anti-inflammatory drug (NSAID). The COX-inhibiting activity resides primarily in the (S)-enantiomer whereas the (R)-enantiomer has scarce COX activity. (R)-Flurbiprofen has been found to inhibit tumor growth in various animal models. In vitro experiments have shown that this effect is based on the induction of a cell cycle block and apoptosis [21]. 

Wu K-D, Cho YS, Katz J, Ponomarev V, Chen-Kiang S, Danishefsky SJ, Moore MAS. Investigation of antitumor effects of synthetic epothilone analogs in human myeloma models in vitro and invivo. Proc. Natl. Acad. Sci. U.S.A. 2005 102 10640-10645. de Jonge M, Verweij J. The epothilone dilenuna. J. Clin. Oncol. 2005 23 9048-9050. 

Despite the wealth of useful information than can be gleaned from in vitro assays measuring a step(s) in the metastatic cascade, the only method for assessing metastatic potential involves the use of in vivo models. In vitro models are simply not of sufficient complexity to recapitulate the multitude of steps of the metastatic process. This is not to demean the usefulness of in vitro models. 

It is interesting to notice that the characterization of the cellular and molecular mechanisms of the star fruit intoxication needs to pass through a group of different experimental protocols among them in vivo and the in vitro bioassays. The correlation between in vivo and in vitro models is then more complex that we should think it is [53]. Thus, the particular case of synaptosomes and GABA and glutamate release and re-uptake, shows neurochemical dynamics associated to star fruit intoxication mechanisms in a preparation which consists of isolated synaptic terminals (44). However, additional studies are needed with brain slices from control brains treated with the AcTx and even the use of ex vivo models in vitro bioassays from tissue after in vivo experiments), for example, in our case, brain slices from treated animals. 

Triglia D, Braa S, Yonan C Naughton G (1991) In vitro toxicity of various classes of test agents using the neutral red assay on a human three-dimensional physiologic skin model. In Vitro Cell and Developmental Biology 21 A 239-244. 

Jayaprakasha, G. K., Singh, R. P., and Sakariah, K. K. (2001). Antioxidant activity of grape seed (Vitis vinifera) extracts on peroxidation models in vitro. Food Chem. 73,285-290. 

Key words Complexity, Computational models, In vitro models, Pathways of toxicity, Pharmacodynamics, Pharmacokinetics, Prediction, Omics data integration, Quantitative extrapolation, Toxicity, Variability... 

W. R. Gillespie, Convolution—based approaches for in vivo in vitro correlation modeling, in vitro in vivo correlations. Adv Exp Med Biol 423 53-65 (1997). 

Blaha, M., Kohl, J., DuBose, D., Bowers, W., Jr., and Walker, J. (2001). Ultrastructural and histological effects of exposure to CEES or heat in a human epidermal model. In Vitro Mol Toxicol 14, 15-23. 

K. Beckenlehner, S. Bannke, T. SpruB, G. Bernhardt, H. Schonenberger, and W. Schiess. Hyaluronidase enhances the activity of adriamycin in breast cancer models in vitro and in vivo. J. Cancer Res. Clin. Oncol. 775 591 (1992). 

Qiao D, Seidler FJ and Slotkin TA (2001). Developmental neurotoxicity of chlorpyrifos modelled in vitro comparative effects of metabolites and other cholinesterase inhibitors on DNA synthesis in PC12 and C6 cells. Environ Elealth Perspect, 109, 909-913. 

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