Respiratory Disease Models

Fibrotic Lung Disease As is the case with the other models of human respiratory disease models, excellent reviews of animal models of fibrotic lung disease are available in the literature. A recent publication from Moore et al. will be briefly outlined in the following (Moore et al., 2013). 

In addition to the NOD mouse, Entelos has models for several human metabolic diseases (diabetes, obesity, and metabolic syndrome), inflammatory diseases (rheumatoid arthritis), and respiratory diseases (asthma and COPD). 

Selgrade, M.K., Air pollution and respiratory disease extrapolating from animal models to human health effects, Immunopharmacology, 48, 319, 2000. 

A series of 7-diazabicycloalkyl quinolones has been prepared and found to exhibit excellent broad spectrum activity against important veterinary pathogenic bacteria [105], The structures of several of these interesting bicyclic analogues (76) as well as MIC data are summarized in Table 6.28. Compound (76e) (danofloxacin), which also exhibits excellent p.o. and s.c. activity in a mouse protection model for Pasteurella multocida [ 106], is undergoing development for use in veterinary medicine. It has been shown to exhibit excellent bioavailability properties in cattle, swine and poultry [107] and is efficacious in models for the treatment of respiratory diseases in food-producing animals [108],... 

A recent review [73] describes the various animal models used to mimic the different aspects of this disease. For KCAs, the in vivo models employed have generally been bronchoconstrictor in nature, where test compounds have been examined for their ability to prevent or reverse an induced bronchoconstriction. This can be achieved in several ways, the simplest being the respiratory embarrassment model, where a guinea-pig is exposed to a concentration of a bronchoconstrictor that causes dyspnoea. The KCAs may be tested by the oral route for their ability to attenuate the onset of dyspnoea. Even in the control animals, in which dyspnoea leads to rapid collapse, removal of the animals from the chamber and away from the bronchoconstrictor agent, allows a full recovery [74]. Various other ways of inducing bronchoconstriction in conscious animals are available, one of the... 

Alterations in the previous respiratory defenses would be expected to make the lung more vulnerable to infectious disease. Animal models have served to demonstrate the effects of airborne chemicals and to establish associations between these effects and actual increases in susceptibility to respiratory disease. These in vivo models combine the adverse effects of the toxicant with the added stress induced... 

Respiratory disease Alveolar macrophages synthesize lipoxins Reduced levels of endogenous lipoxin observed in asthma and COPD LX administration to a murine model of asthma blocked airway hyper-responsiveness and pulmonary inflammation Kim et al. 1988 Vaichier et al. 2005 Levy et al. 2002... 

The longitudinal course of the targeted disease is of particular interest in many chronic ailments where conditions worsen over time, including Alzheimer s disease, Parkinson s disease, osteoporosis, diabetic nephropathy, and respiratory disease (14). Alternative models have been developed for other disease states where cyclical effects may be observed, such as depression (15) or myelosuppression (5). Included in longitudinal models are descriptions for the natural progression of disease as well as nonpharmacological intervention (e.g., placebo treatment). 

METZGER, W.J., ZAVALA, D RICHERSON, H.B., MOSELEY, P IWAMOTO, P MONICK, M SJOERDSMA, K. HUNNINGHAKE, G.W. (1987) Local allergen challenge and bronchoalveolar lavage of allergic asthmatic lungs description of the model and local airway inflammation. American Review of Respiratory Disease, 135,433 440. 

The observation that T-cell immune responses may be involved in the pathogenesis of occupational respiratory diseases is supported by animal models (Dearman et al., 1992). Rodents can be easily sensitized to LMW chemicals such as acid anhydrides and diisocyanates. A murine model has been used to study the differential production of cytokines by helper T-cell subsets (Thl and Th2) after exposure to different reactive chemicals. It has been shown that under normal conditions Thl lymphocytes primarily secrete IL-2, interferon-/and tumour necrosis factor J3 (TNI -/ ) whereas Th2 lymphocytes secrete IL-4, IL-5, IL-10 and IL-13. A predominance of Th2 cells correlated with IgE-mediated immune responses, while a predominance of Thl cells was associated with cell-mediated immune responses (Dearman et al., 1992). These investigators demonstrated preferential activation of Th2 cells by phthalic anhydride (PA), trunellitic anhydride (TMA) and diphenyl-methylene diisocyanate, indicating that chemical structure may be important for determining the quality of immune response elicited (Dearman et al., 1992). 

BIAGINI, R.E., MOORMAN, W.J., LEWIS, T.R. BERNSTEIN, I.L. (1986) Ozone enhancement of asthma in a primate model. American Review of Respiratory Disease, 134, 719-725. 

OBATA, H TAO, Y KIDO, M NAGATA, N TANAKA, I. KUROIWA, A. (1992) Guinea pig model of immunologic asthma induced by inhalation of TMA. American Review of Respiratory Disease, 146, 1553-1558. 

Respiratory syncytial virus (RSV) and parainfluenza virus (PIV) are leading causes of respiratory disease in infants, young children, immuno-compromized patients, and the elderly. Bitko et al. [140] used viral-specific siRNAs for the treatment of these respiratory syndromes in an animal model. In this study, either, or both, viral infections could be specifically prevented and inhibited when corresponding siRNAs were infused intranasally in mice, with or without transfection reagents. These investigators noted an excellent correlation between the activities observed in their siRNAs in in vitro cell cultures and those observed in their animal model. This type of approach presents a fast screen for efficient siRNA sequences before more expensive and demanding applications are pursued in animals. In addition, nasal administration of siRNA compounds seems to provide a convenient... 

Most chronic illness confronts patients and caregivers with changes in daily life and changes in social relations. They produce disability, often with exacerbations. Medical care is usually continuous and, in the case of the patients with respiratory diseases, is also supported by devices such as oxygen or ventilators (2). Facing the final phases of life is another difficult, added pressure. Most patients with chronic illness require support from a variety of health care professionals, often situated in different health facilities. In the chronic care model, it is crucial to evaluate the patient in a stable situation to establish plans of action for the exacerbations, to promote self-management, and to have a good information system. 

Ginkgolide B is a selective antagonist of platelet aggregation induced by platelet-activating factor (PAF). PAF, an inflammatory autacoid, is involved in various inflammatory, cardiovascular, and respiratory disorders. " Ginkgo extract has also displayed anti-inflam-matroy activity in a number of conditions and disease models such as colitis, arthritis, skin inflammation, and rat paw edema. " Antiinflammatory mediators have been suppressed by the extract. ... 

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