Animal Models degenerative diseases

For assessment of degenerative joint disorders as potential side effects of drugs under investigation, a multitude of animal models for osteoarthritis is available, and their respective suitability for the pleiotropic disease aspects have been recently described and discussed by Oegema and Visco (1999), van den Berg (2001), and Brandt (2002). However, novel therapeutic principles, like e.g. the matrix metalloproteinases, have revealed their musculoskeletal side effects as late as in clinical studies only, which then retraced the focus of drug developmental steps back to scrutinize and refine existent models for different applications (Jacobson et al. 1999 Renkiewicz et al. 2003 Peterson 2004). 

These techniques are easily employed in generating temporal expression patterns. The only requirement is the proper design of experiments. In that context, appropriate animal models of degenerative diseases must be used,... 

Methods such as Shannon entropy will be needed in future studies of degenerating and regenerating tissue. Entropy may be used to select out the most likely drug target candidates from data on animal models of Alzheimer s and other degenerative diseases. Similarly, we can study the regeneration of animal tissues that fail to regenerate in humans (e.g., spinal... 

Interestingly, many more lycopene-based studies have been conducted in animal models or in human subjects rather than in cell culture. The explanation for this may be seen as two-fold. Firstly, because of the high lipophilic nature of lycopene, it is most commonly solubilized in tetrahydrofuran, which, in itself, is toxic to cells. Second, since lycopene, a phytochemical, is a natural product and, in most studies, was either supplied to subjects in its natural form (tomato juice, etc.) rather than supplements or indirectly deduced from dietary questioimaires, ethical committee approval was relatively easy to obtain. Substantial evidence has been produced relating the consumption of lycopene to a decreased risk of acquiring degenerative diseases, such as certain kinds of cancers and cardiovascular disease. In addition, the usefulness of lycopene has, on several accounts, been shown in the treatment of cancers. Thus it becomes increasingly important to understand in detail the molecular mechanism of action of lycopene in varions model cell systems. 

There are multitudes of namrally occurring diseases of the central nervous system, including degenerative, traumatic, neoplastic, and metabolic disorders. Naturally occurring diseases for which there are potential models include models for include Parkinson s disease (PD), Huntington s disease (HD), Alzheimer s disease (AD), cerebral ischemia, miscellaneous neoplastic conditions, and lysosomal storage diseases. Examples of selected animal models of human disease will be briefly suimnarized. 

The first report that a copper (Cu) complex was effective in the treatment of rheumatoid and other degenerative connective tissue diseases appeared in 1941. Since the first study of Cu complexes in an animal model of inflammation was not carried out until 1950, their use in human therapy preceded pharmacologic evaluation by about 10 yr. Subsequent demonstrations that Cu complexes have anti-inflammatory activity in many animal models of inflammation provides support for the earlier claims that they were effective in treating rheumatoid and other degenerative connective tissue diseases in man. 

Two developments led neuroscientists as well to reexamine aluminum as a potential neurotoxicant. One was the discovery that aluminum played a role in the encephalopathy associated with kidney dialysis. The other was the implication that it was associated with senile dementia of the Alzheimer type. The connection with dialysis encephalopathy has been established, although a suitable animal model is lacking. The association with Alzheimer s disease is tenuous, but the issue has stimulated a considerable body of work that both illuminates the biological actions of aluminum and provides further knowledge of degenerative processes in the nervous system. The behavioral data in laboratory animals are ambiguous because, to achieve effects, many experimenters have administered the aluminum intracranially, a mode of administration with obvious pitfalls. A useful summary of the recent literature appears in the volume edited by Liss. ... 

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