Animal models aspects

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. 

Although many animal models for iron overload exist, some mimicking certain aspects of HH, the 32-microglobulin knockout mouse is of special interest as it revealed for the first time crucial aspects of the pathogenesis of human HH in an animal model, and also because it underlines the important links between iron metabolism and the immune system. Hepatic iron overload in 32-microglobulin ( 32m)-deficient mice appeared to be similar to that found in HH, with pathological iron depositions occurring predominantly in liver parenchymal cells (de Sousa et ah,... 

Investigations of regional differences in permeability and metabolism have been carried out using a variety of animal models [22, 29, 75, 102, 109, 112, 137]. Animal tissues (mainly from rats) are widely used in the Ussing chamber to investigate intestinal transport of drugs, and regional aspects [29, 75, 138], whereas few studies have been conducted with human tissues due to their limited availability. 

Some aspects of multiple sclerosis are reflected in the animal model experimental autoimmune encephalomyelitis, which is induced by immunization of susceptible animals with appropriate encephalogenic proteins or peptides. In these animals, if cultured adult stem cell neurospheres are injected into the bloodstream, injected cells can find their way to damaged portions of the nervous system and improve function in mice. How the injected cells augmented the recovery process is unclear. One possibility is that cells recruited to the lesions differentiated into oligodendrocytes and generated new myelin sheaths, but this seems unlikely in the face of ongoing cellular destruction. 

In addition to toxicity and safety data, the preclini-cal package to start clinical studies also contains information on the pharmacology, the pharmacokinetics and metabolism and the galenical aspects of the compound. As a rule there is evidence of pharmacological activity and, if possible, of therapeutic activity in one or more animal models of disease. Ideally there is also information on the in vivo concentration effect relationship. 

Search for and validate animal models to analyse toxicological aspects of reproductive biology to develop appropriate systems that are reproducible, low cost and easier to extrapolate to human disease. 

Anandamide was shown to alleviate nociception in several behavioral animal models, e.g. the hot plate and formalin test (Calignano et al., 2001). A most interesting aspect of anandamide with respect to pain research is that it seems to bind to the hypothetical third cannabinoid receptor (Di Marzo et al., 2000b) In the hot plate test anandamide is still antinociceptive in CB/ mice, which is consistent with the observation that the selective CBi receptor antagonist SR 141716A does not block motor inhibitory and antinociceptive effects of anandamide in wild-type mice. 

An accurate animal model is important for the advancement of technology for noninvasive glucose sensing. Such a model enables control over important aspects of the experiment, such as control over in vivo glucose concentrations and the ability to set the rate and direction of glycemic changes. 

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