Phase 2a, AMP Challenge, Dose Escalation Study to Assess the Dose Response for Topical Efficacy and Systemic Activity in Asthmatic Subjects

Condition:   Asthma
Interventions:   Drug: Fluticasone furoate (FF) Dry Powder Inhaler;   Drug: Fluticasone propionate (FP) Dry Powder Inhaler;   Drug: Budesonide (BUD) Turbuhaler;   Drug: Placebo (ELLIPTA or DISKUS)
Sponsor:   GlaxoSmithKline
Not yet recruiting – verified December 2016

View full post on ClinicalTrials.gov: asthma | Studies received in the last 14 days

Effect of compound Maqin decoction on TGF-?1/Smad proteins and IL-10 and IL-17 content in lung tissue of asthmatic rats.

Effect of compound Maqin decoction on TGF-?1/Smad proteins and IL-10 and IL-17 content in lung tissue of asthmatic rats.

Genet Mol Res. 2016 Sep 2;15(3):

Authors: Xie YH, Li XP, Xu ZX, Qian P, Li XL, Wang YQ

Abstract
In this research, compound Maqin decoction (CMD) has been shown to positively affect in airway inflammation of asthma models. We evaluated the effects of CMD on the expression of transforming growth factor (TGF)-?1/Smad proteins, interleukin (IL)-17, and IL-10 in lung tissue of asthmatic rats. Asthma was induced in a rat model using ovalbumin. After a 4-week treatment with CMD, rats were killed to evaluate the expression of TGF-?1 and Smad proteins in lung tissue. IL-10 and IL-17 levels in lung tissue homogenates were determined by ELISA. The expression of TGF-?1 and Smad3 protein increased, whereas expression of Smad7 protein decreased upon high-dose or low-dose treatment with CMD or by intervention with dexamethasone, compared to the control. There was a significant difference between treatment with a high dose CMD and the control treatment, but no significant difference was found between high-dose CMD treatment and dexamethasone intervention. The expression of TGF-?1 and Smad7 protein increased, whereas the expression of Smad3 protein decreased in the model group compared to other groups. In the CMD high-dose group, low-dose group, and dexamethasone intervention group, the IL-17 concentrations in lung tissue homogenates were decreased, while IL-10 levels were increased. Again, there was a significant difference between CMD high-dose and control treatment, but not between CMD high-dose treatment and dexamethasone intervention. Thus, positive effects of CMD against asthmatic airway remodeling may be due to its regulatory effect on TGF-?1, Smad3, and Smad7 protein levels and on cytokines such as IL-10 and IL-17.

PMID: 27706676 [PubMed – in process]

View full post on pubmed: asthma

Pentoxifylline and its active metabolite lisofylline attenuate transforming growth factor ?1-induced asthmatic bronchial fibroblast-to-myofibroblast transition.

Pentoxifylline and its active metabolite lisofylline attenuate transforming growth factor ?1-induced asthmatic bronchial fibroblast-to-myofibroblast transition.

Acta Biochim Pol. 2016 Jul 30;

Authors: Wójcik-Pszczo?a K, Hi?cza K, Wnuk D, K?dzio?ka D, Koczurkiewicz P, Sanak M, Madeja Z, P?kala E, Michalik M

Abstract
Bronchial asthma is characterized by persistent airway inflammation and airway wall remodeling. Among many different cells and growth factors triggering changes in bronchi structure, transforming growth factor ?1-induced fibroblast to myofibroblast transition is believed to be very important. The aim of this study was to evaluate whether theophylline (used in asthma therapy) and two other methylxanthines (pentoxifylline and its active metabolite lisofylline), may affect transforming growth factor ?1-induced fibroblast to myofibroblast transition in bronchial fibroblasts derived from asthmatic patients. We show here for the first time that selected methylxanthines effectively reduce transforming growth factor ?1-induced myofibroblast formation in asthmatic bronchial fibroblast populations. PTX was found to be the most effective methylxanthine. The number of differentiated myofibroblasts after PTX, LSF and THEO administration was reduced at least twofold. Studies on the use of methylxanthines opens a new perspective in the development of novel strategies in asthma therapy through their two-pronged, anti-inflammatory and anti-fibrotic action. In the future they can be considered as promising anti-fibrotic drugs.

PMID: 27474406 [PubMed – as supplied by publisher]

View full post on pubmed: asthma