Vitro Model Studies

A final aspect of this topic which should be mentioned is the apparent failure of hexosaminidase which is present in high concentration in fetal calf serum (—2000 units/ml) to cross the plasma membrane of cultured skin and amnio tic cells. Fetal calf serum is usually added to 

Bemheimer, H., and Karbe, E., 1970, Morphologische und neurochemische Untersuchun-gen von 2 Formes der amaurotischen Idiotic des Hunds Nachweis einer Gm2 Gangliosidose, Acta Neuropath. 16 243. 

Hereditary diseases—Causes, cures, and problems, Angew Chem. Intern. Ed. 12 1. 

Kanfer, J. N., and Shapiro, D., 1965, The metabolism of glucocerebrosides II. Evidence of an enzymatic deficiency in Gaucher s disease, Biochem. Biophys. Res. Commun. 18 221. 

O Brien, J. S., Bradley, R. M., and Gal, A. E., 1970, Sphingolipid hydrolases in brain tissue of patients with generalized gangliosides, Biochem. Biophys. Acta 210 194. 

---

A concerted effort is needed to increase our understanding of the transfer and uptake of reactive gases in the lung. A program in this field should involve in vitro model studies, animal experiments, and clinical studies. More information is required on the chemical, physical, and morphologic properties of the mucous layer and the kinetics of the reactions of ozone in the mucous and tissue layers. Experimental data on uptake and dosage for ozone and other oxidants are difficult to obtain for the tracheobronchial and pulmonary regions. Such data for animals and humans will be needed to test the present simple transport models, before further refinements are made. 

Boxberger, H. J., Paweletz, N., Spiess, E. and Kriehuber, R. (1989). An in vitro model study of BSp73 rat tumor cell invasion into endothelial monolayer. Anticancer Res. 9, 1777-1786. 

In the human body are produced a range of reactive oxygen species, including 02, OH, 02, and H2O2 [53]. In vitro model studies aim at mimicking in vivo systems. The interaction of carotenoids with other dietary antioxidants have been studied, including vitamin C (ascorbic acid) and vitamin E (tocopherol, TOH) [54-56], In the model proposed, the carotenoid (Car) is repairing vitamin E ... 

Keynton, R.S., Rittgers, S.E., and Shu, M.C.S. 1991. The effect of angle and flow rate upon hemodynamics in distal vascular graft anastomoses An in vitro model study. ASME J. Biomech. Eng. 113 458-463. Kim, S.H., Chandran, K.B., and Chen, C.J. 1992. Numerical simulation of steady flow in a two-dimensional total artificial heart model. ASME J. Biomech. Eng. 114 497-503. 

In contrast. Mole and Waterman (147), using in vitro model studies, have demonstrated that both hydrolyzable and condensed tannins may stimulate tryptic hydrolysis due to tannin-induced structural changes in the substrate protein. Condensed tannins have also been shown to possess algicidal activity (18). Much work remains to be done on the ecological role of tannins, which should be a fruitful field of research now that tannins of defined structure are readily available. 

Im Hof V, Gehr P, Gerber V, Lee MM, Schurch S. In vivo determination of surface tension in the horse and in vitro model studies. Respir Physiol 1997 109 81 93. 

Chemical Antioxidant Systems. The antioxidant activity of tea extracts and tea polyphenols have been determined using in vitro model systems which are based on hydroxyl-, peroxyl-, superoxide-, hydrogen peroxide-, and oxygen-induced oxidation reactions (109—113). The effectiveness of purified tea polyphenols and cmde tea extracts as antioxidants against the autoxidation of fats has been studied using the standard Rancimat system, an assay based on air oxidation of fats or oils. A direct correlation between the antioxidant index of a tea extract and the concentration of epigallocatechin gallate in the extract was found (107). 

In-vitro models can provide preliminary insights into some pharmacodynamic aspects. For example, cultured Caco 2 cell lines (derived from a human colorectal carcinoma) may be used to simulate intestinal absorption behaviour, while cultured hepatic cell lines are available for metabolic studies. However, a comprehensive understanding of the pharmacokinetic effects vfill require the use of in-vivo animal studies, where the drug levels in various tissues can be measured after different dosages and time intervals. Radioactively labelled drugs (carbon-14) may be used to facilitate detection. Animal model studies of human biopharmaceutical products may be compromised by immune responses that would not be expected when actually treating human subjects. 

The use of mierobial systems as in vitro models for dmg metabohsm in humans has been proposed sinee there are many similarities between certain microbial enzyme systems and mammalian liver enzyme systems. The major advantages of using miero-organisms is their ability to produce significant quantities of metabohtes that would otherwise be diffieult to obtain from animal systems or by chemical synthesis, and the considerable reduetion in operating costs compared with animal studies. 

Of course, the term proven efficacy is central to any resource investment in this area. Basic information on time and dose responses in humans to complex foods rich in carotenoids (and other phytochemicals) is pitifully small. Much of our information is based upon inadequate databases derived from chemical analysis, in vitro models that have not been properly evaluated or validated, and short-term, high-dose human studies. Future research progress requires much more rigorous debate on the experimental systems employed... 

Isab, A.A., Shaw, C.E. Ill and Locke, J. (1988) GC-MS and oxygen-17 NMR tracer studies of triethylphosphine oxide formation from auranofin and water- O in the presence of bovine serum albumin an in vitro model for auranofin metabolism. Inorganic Chemistry, 27, 3406-3409. 

The importance of drug ionization using cell-based methods such as Caco-2 in the in vitro prediction of in vivo absorption was discussed [45]. It was observed that when the apical pH used in Caco-2 studies was lowered from 7.4 to 6.0 a better correlation was obtained with in vivo data, demonstrating that careful selection of experimental conditions in vitro is crucial to produce a reUable model. Studies with Caco-2 monolayers also suggested that the ionic species might contribute considerably to overall drug transport [46]. 

Avdeef, A., Strafford, M., Block, E., Balogh, M. P., Chambliss, W., Khan, I. Drug absorption in vitro model filter-immobilized artifidal membranes 2. Studies of the permeability properties of lactones in Piper methysticum Forst. Eur.J. Pharm. Sci. 2001, 14, 271-280. 

Whereas the relationship of solute permeability with lipophilicity has been studied in a large number of in vivo systems (including intestinal absorption models [54,55], blood-brain [56 58] and blood nerve [59] barrier models, and cell culture models [60 62], to name just a few), numerous in vitro model systems have been developed to overcome the complexity of working with biological membranes [63-66]. Apart from oil-water systems that are discussed here, the distribution of a solute between a water phase and liposomes is... 

The strategy for the development of the oral absorption model at pION is illustrated in Fig. 7.58. The human jejunal permeabilities reported by Winiwarter et al. [56] were selected as the in vivo target to simulate by the in vitro model. In particular, three acids, three bases and two nonionized molecules studied by the University of Uppsala group were selected as probes, as shown in Fig. 7.58. They are listed in the descending order of permeabilities in Fig. 7.58. Most peculiar in the ordering is that naproxen, ketoprofen, and piroxicam are at the top of the list, yet these three acids are ionized under in vivo pH conditions and have lipophilicity (log Kj) values near or below zero. The most lipophilic molecules tested, verapamil and carbamazepine... 

An In Vitro Model to Study Intestinal Absorption of Carotenoids.370... 

The Caco-2 cell line was isolated from a human colon carcinoma, and has been characterized as one of the best in vitro models of intestinal epithelium. Indeed, in contrast to other intestinal cell lines, Caco-2 cells are able to constitute a homogenous monolayer and to spontaneously differentiate into polarized cells, highly similar to human mature enterocytes, after approximately 2 weeks of culture. Furthermore, the Caco-2 cells present microvillosities at the apical side and have a high transmembrane resistivity, which confirms the fact that the cells are confluent and link to one another via gap junctions. Finally, they can absorb different compounds, express many enzymes involved in intestinal metabolic pathways (Pinto et al. 1983, Musto et al. 1995, Salvini et al. 2002), and give reproducible in vitro results consistent with results obtained in in vivo studies (Artursson and Karlsson 1991). 

Miki, J and JS Rhim. 2007. Prostate cell cultures as in vitro models for the study of normal stem cells and cancer stem cells. Prostate Cancer Prostatic Dis 11(1 ) 32—39. 

According to the authors, no study has previously been setup to investigate the potential hepatotoxicity of leachate using in vitro models. Results from the in vitro study (Fig. 4) clearly indicate that the inhibition of cell proliferation by the raw... 

In vitro models could be used to study the molecular mechanisms involved in the process of neoplastic transformation and as screening tools for the classification of the carcinogenic potential of a substance. Among the in vitro tests available to the scientific community, the CTA may represent an important tool for the identification of carcinogens, particularly those that are not identifiable by classic mutagenicity tests such as the Ames test. 

Recently, the toxicological responses of CNTs in the intra-abdominal cavity have attraded significant attention. Studies have been carried out mainly in vivo, and only three in vitro models have been tested. The significance of these studies is unknown, however, since no evidence indicating that CNTs can reach the pleural space is currently available. 

In summary, the in vivo protective effects of Tyv-specific antibodies, exclusion and immobility, can now be effectively studied using an in vitro model of the intestinal epithelium. Larvae are prevented from entering epithelial cells by caps of immune complexes or by binding of antibody to Tyv in the absence of immune complex formation. These effects would correlate with exclusion of larvae from epitheha observed in passively immunized rats. Larvae are encumbered as they migrate within epithelial monolayers, an effect that may correlate with immobility of larvae observed in vivo. It is reasonable to conclude that in the animal host the different effects work in combination, most iikeiy in cooperation with innate host defences, to cause nematode expuision from the intestine. 

---