Animal models for anti-emphysema drug discovery.

Introduction: Emphysema is characterized by an abnormal and permanent enlargement of airspaces accompanied by destruction of their walls. Up to now, there is no cure for emphysema, and animal models may be important for new drug discovery.

Areas Covered: Herein, the authors review animal models of emphysema since the protease-antiprotease hypothesis as well as the results obtained with compounds tested in these models.

Downregulation of NOX4 expression by roflumilast N-oxide reduces markers of fibrosis in lung fibroblasts.

The phosphodiesterase 4 inhibitor roflumilast prevents bleomycin- (BLM-) induced lung fibrosis in animal models. However, its mechanism of action remains unknown. We investigated whether roflumilast N-oxide (RNO), the active metabolite of roflumilast, can modulate in vitro the oxidative effects of BLM on human lung fibroblasts (HLF).

Individuals' decision to co-donate or donate alone: an archival study of married whole body donors in Hawaii.

Background: Human cadavers are crucial to numerous aspects of health care, including initial and continuing training of medical doctors and advancement of medical research. Concerns have periodically been raised about the limited number of whole body donations. Little is known, however, about a unique form of donation, namely co-donations or instances when married individuals decide to register at the same time as their spouse as whole body donors.

Reactivity of mouse alveolar macrophages to cigarette smoke is strain dependent.

Cigarette smoke (CS) is a main risk factor in chronic obstructive pulmonary disease (COPD), but only 20% of smokers develop COPD, suggesting genetic predisposition. Animal studies have shown that C57BL/6J mice are sensitive to CS and develop emphysema, whereas Institute of Cancer Research (ICR) mice are not. To investigate the potential factors responsible for the different susceptibility of ICR and C57BL/6J mice to CS, we evaluated in alveolar macrophages (AMs) isolated from these strains of mice the possible mechanisms involved in the inflammatory and oxidative responses induced by CS.

Effect of roflumilast on inflammatory cells in the lungs of cigarette smoke-exposed mice.

Background: We reported that roflumilast, a phosphodiesterase 4 inhibitor, given orally at 5 mg/kg to mice prevented the development of emphysema in a chronic model of cigarette smoke exposure, while at 1 mg/kg was ineffective. Here we investigated the effects of roflumilast on the volume density (VV) of the inflammatory cells present in the lungs after chronic cigarette smoke exposure.

Methods: Slides were obtained from blocks of the previous study and VV was assessed immunohistochemically and by point counting using a grid with 48 points, a 20x objective and a computer screen for a final magnification of 580x.