General Inflammation Models

Several immune-regulated models have been described, of which the delayed-type hypersensitivity reaction in the skin is an example. In several species application of allergic or con-tact-sensitizing substances results in a local inflammatory reaction involving adhesion mole- 

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The molecular mechanism linking the inflammatory response to redox equilibria and modification of nitric oxide production will be explored in an animal model system of septic shock, a generalized inflammation induced by bacterial lipopolisaccharide (LPS). It is known that endotoxemia induces a complex interplay between the activation of nuclear transcription factors such as nuclear factor kappa B (NFkB) and a cascade-activation of various enzymatic activities, mostly mediators of the inflammatory response with particular attention to the variation of the inducible form of nitric oxide synthase (iNOS). 

Schreiber s model has also proved to be a general approach to a series of oxygenated metabolites of arachidonic acid, such as lipoxin A and lipoxin B.50 The family of linear oxygenated metabolites of arachidonic acid has been implicated in immediate hypersensitivity reactions, inflammation, and a number of other health problems. Among these metabolites, several compounds, such as lipoxin A, lipoxin B, 5,6-diHETE, and 14,15-diHETE possess 1-substituted (/ )-1 -alken-3.4-diol 84 as a common substructural moiety. Therefore, the car-binol 83 is an ideal substrate for generating compound 84 by applying Sharpless epoxidation reaction.50... 

Many animal models have been described in which inflammation is induced and activation of the endothehum occurs. Here, some disease-specific models, in addition to some general inflammatory experimental models will be summarized. 

Containing Experiments on Factitious Air. His presentation is a model of clarity and simplicity well illustrated by his opening sentence By factitious air, I mean in general any kind of air which is contained in other bodies in an unelastic state, and is produced from thence by art. In the three parts Cavendish describes his experiments relating to inflammable air, fixed air, and the air produced by fermentation and putrefaction. 

Various studies have also examined animal models of pulmonary inflammation that are representative of primary eosinophil or neutrophil infiltration. Lung inflammation characterized by eosinophil influx has been used as a model of asthma and is not generally associated with lung fibrosis. After several episodes of repeated antigen challange, a subset of Ascaris -sensitive Cynomolgus monkeys developed a persistent eosinophilia and enhanced intercellular adhesion molecule-1 (ICAM-1) expression on pulmonary endothelial and epithelial cells when compared to control animals (Gundel etal., 1991, 1992). 

Validated models or strategies to assess or identify chemical or physical factors that induce autoimmune diseases are not available (see also chapter 10). Despite the fact that methods (e.g. detection of autoantibodies, histopathology) exist that could be used in a general 28-day toxicity study, potential autoimmunogenicity is usually missed. Nevertheless, any sign of inflammation in any of the animals in a 28-day study should be regarded as an alert of hazard. A chemical that produces elevated autoantibodies in experimental animals or exacerbates autoimmune disease in autoimmune-prone animals (i.e. increases severity of disease or lessens time to occurrence) is also of concern because of its potential to cause autoimmunity in humans. This is because the molecular and cellular events responsible for autoimmune disease are similar in experimental animals and humans. However, at this time, it is not possible to determine the predictive value of these models. The assumption that, for chemical-induced autoimmunity, humans are at least as sensitive as animals is a conservative estimate of sensitivity. 

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