Population modeling, potential role

Chapter 11 Potential Role of Population Modeling in the Regulatory... 

The parameters we used for density-dependent regulation could not be underpinned with data from the literature the main role of the density dependence in the model was to keep populations at a desired density level without affecting the population s potential for recovery from very low densities too much. 

Although they remain less effective than inhaled corticosteroids, a 5-LOX inhibitor (zileuton) and selective antagonists of the CysLTl receptor for leukotrienes (zafirlukast, montelukast, and pranlukast see Chapter 20) are used clinically in mild to moderate asthma. Growing evidence for a role of the leukotrienes in cardiovascular disease has expanded the potential clinical applications of leukotriene modifiers. Conflicting data have been reported in animal studies depending on the disease model used and the molecular target (5-LOX versus FLAP). Human genetic studies have demonstrated a link between cardiovascular disease and polymorphisms in the leukotriene biosynthetic enzymes, in particular FLAP, in some populations. 

Based on the short overview of the known animal models relevant to autoimmune diseases, it is quite clear the task of hazard identification and risk assessment for potential drug-induced autoimmunity is presently very difficult. There is no single in vivo model that can be used routinely to evaluate new drugs for autoimmunity induction. Nevertheless, some of the models could possibly be applied to test therapeutics with specific properties (e.g., off-target immunoregulatory activity) and concerns (e.g., patient population) in order to gain additional perspective and understanding of their role in autoimmune responses. 

Obesity is associated with impaired immunity (Fried et al, 1998 Tanaka et al, 1993 Visser et al, 1999) and as suggested by Ekesbo et al. (2000) obesity might be the indicator for increased susceptibility to H. pylori and CP infection (Ekesbo et al., 2000). However, Dart et al. (2002) found no preponderance of antibodies to Chlamydia trachomatis and Chlamydia pssit-taci in the same subject population. Lack of relationship of BMI with prevalence of antibodies to C. trachomatis and C. pssittaci indicated that increased BMI did not necessarily predispose the subjects to catch infection. Experiments with animal models designed to investigate the adipogenic potential of CP and human sero-epidemiological data are needed to further determine the role of CP in obesity. 

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