The efficacy and safety of pinocembrin in a sheep model of bleomycin-induced pulmonary fibrosis.

The primary flavonoid, pinocembrin, is thought to have a variety of medical uses which relate to its reported anti-oxidant, anti-inflammatory, anti-microbial and anti-cancer properties. Some studies have reported that this flavonoid has anti-fibrotic activities. In this study, we investigated whether pinocembrin would impede fibrosis, dampen inflammation and improve lung function in a large animal model of pulmonary fibrosis.

Tetrathiomolybdate Treatment Attenuates Bleomycin-Induced Angiogenesis and Lung Pathology in a Sheep Model of Pulmonary Fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a progressive chronic lung disease characterized by excessive extracellular matrix (ECM) deposition in the parenchyma of the lung. Accompanying the fibrotic remodeling, dysregulated angiogenesis has been observed and implicated in the development and progression of pulmonary fibrosis. Copper is known to be required for key processes involved in fibrosis and angiogenesis.

Small airway remodeling in a sheep model of bleomycin-induced pulmonary fibrosis.

Background: Although IPF is described traditionally as a disease affecting lung parenchyma, there is renewed interest in the alterations in the structure and function of the small airways in both IPF patients, and animal models of pulmonary fibrosis. Small airway remodeling may contribute to the pathophysiology of pulmonary fibrosis. Given the dearth of knowledge of small airway changes in pulmonary fibrosis, this study aims to assess the structural remodeling, as well as functional changes associated with bleomycin-injured small airways in a sheep model of pulmonary fibrosis.

K3.1 channel blockade attenuates microvascular remodelling in a large animal model of bleomycin-induced pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a chronic progressive lung disease with limited therapeutic options and poor prognosis. IPF has been associated with aberrant vascular remodelling, however the role of vascular remodelling in pulmonary fibrosis is poorly understood. Here, we used a novel segmental challenge model of bleomycin-induced pulmonary fibrosis in sheep to evaluate the remodelling of the pulmonary vasculature, and to investigate the changes to this remodelling after the administration of the K3.

The efficacy of pirfenidone in a sheep model of pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a chronic progressive fibrotic lung disease with unknown cause. While the drugs nintedanib and pirfenidone have been approved for the treatment of IPF, they only slow disease progression and can induce several side-effects, suggesting that there is still an unmet need to develop new efficacious drugs, and interventions strategies, to combat this disease. We have recently developed a sheep model of pulmonary fibrosis for the preclinical testing of novel anti-fibrotic drugs.

Inhibition of the K3.1 Channel Alleviates Established Pulmonary Fibrosis in a Large Animal Model.

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive disease of increasing prevalence marked by poor prognosis and limited treatment options. Ca-activated K3.1 potassium channels have been shown to play a key role in the aberrant activation and responses to injury in both epithelial cells and fibroblasts, both considered key drivers in the fibrotic process of IPF.

Structural and functional correlations in a large animal model of bleomycin-induced pulmonary fibrosis.

Background: Idiopathic pulmonary fibrosis (IPF) is a severe and progressive respiratory disease with poor prognosis. Despite the positive outcomes from recent clinical trials, there is still no cure for this disease. Pre-clinical animal models are currently largely limited to small animals which have a number of shortcomings.

A novel segmental challenge model for bleomycin-induced pulmonary fibrosis in sheep.

Background: Idiopathic Pulmonary fibrosis (IPF) is a fatal respiratory disease, characterized by a progressive fibrosis and worsening lung function. While the outcomes of recent clinical trials have resulted in therapies to slow the progression of the disease, there is still a need to develop alternative therapies, which are able to prevent fibrosis.

Aim: This study uses a segmental lung infusion of bleomycin (BLM) to investigate pulmonary fibrosis in a physiologically relevant large animal species.

Nebulized perflubron and carbon dioxide rapidly dilate constricted airways in an ovine model of allergic asthma.

Background: The low toxicity of perfluorocarbons (PFCs), their high affinity for respiratory gases and their compatibility with lung surfactant have made them useful candidates for treating respiratory diseases such as adult respiratory distress syndrome. We report results for treating acute allergic and non-allergic bronchoconstriction in sheep using S-1226 (a gas mixture containing carbon dioxide and small volumes of nebulized perflubron). The carbon dioxide, which is highly soluble in perflubron, was used to relax airway smooth muscle.

Persistent bronchiolar remodeling following brief ventilation of the very immature ovine lung.

Children and adults who were mechanically ventilated following preterm birth are at increased risk of reduced lung function, suggesting small airway dysfunction. We hypothesized that short periods of mechanical ventilation of very immature lungs can induce persistent bronchiolar remodeling that may adversely affect later lung function. Our objectives were to characterize the effects of brief, positive-pressure ventilation per se on the small airways in very immature, surfactant-deficient lungs and to determine whether the effects persist after the cessation of ventilation.

Lung function in developing lambs: is it affected by preterm birth?

Children born before term often have reduced lung function, but the effects of preterm birth alone are difficult to determine owing to iatrogenic factors such as mechanical ventilation. Our objective was to determine the effects of preterm birth alone on airway resistance, airway reactivity, and ventilatory heterogeneity as an index of intrapulmonary gas mixing. Preterm birth was induced in sheep 12 days before term; controls were born at term ( approximately 147 days).

Immune response to allergens in sheep sensitized to house dust mite.

Background: House dust mite (HDM) allergens are a major cause of allergic asthma. Most studies using animal models of allergic asthma have used rodents sensitized with the 'un-natural' allergen ovalbumin. It has only recently been recognized that the use of animal models based on HDM provide a more relevant insight into the allergen-induced mechanisms that underpin human allergic disease.

Postnatal growth rate, but not mild preterm birth, influences airway structure in adult sheep challenged with house dust mite.

The authors recently showed that preterm birth per se, in the absence of assisted ventilation or elevated inhaled oxygen levels, alters the structure of the airway walls in young lambs. The initial aim of the present study was to determine whether these changes persist into adulthood. Preterm (P; n = 7) lambs were delivered 14 days before term and compared with control lambs (C; n = 8) born at term ( approximately 147 days).

Lung parenchyma at maturity is influenced by postnatal growth but not by moderate preterm birth in sheep.

Background: We have recently shown that moderate preterm birth, in the absence of respiratory support, altered the structure of lung parenchyma in young lambs, but the long-term effects are unknown.

Objectives: To determine whether structural changes persist to maturity, and whether postnatal growth affects lung structure at maturity in sheep.

Methods: At approximately 1.

Claims of current inhaled corticosteroid patents for treating asthma.

The advent and evolution of corticosteroid treatment strategies over the preceding decades means that asthma is now at least controllable for the majority of asthmatics. The main mode of action for corticosteroids is the inhibition of the nuclear factor-kappaB (NF-kappaB) pathway which dampens the pulmonary inflammatory response associated with asthma pathology. The effectiveness of these drugs and the growing market means that there is strong competitive pressure for pharmaceutical companies to improve, or at the very least maintain, their intellectual property position in corticosteroid treatments for asthma.