ABSTRACT
Background: Cystic Fibrosis causing mutations in the gene CFTR , reduce the activity of the CFTR channel protein, and leads to mucus aggregation, airway obstruction and poor lung function. A role for CFTR in the pathogenesis of other muco-obstructive airway diseases such as Chronic Obstructive Pulmonary Disease (COPD) has been well established. The CFTR modulatory compound, Ivacaftor (VX-770), potentiates channel activity of CFTR and certain CF-causing mutations and has been shown to ameliorate mucus obstruction and improve lung function in people harbouring these CF-causing mutations. A pilot trial of Ivacaftor supported its potential efficacy for the treatment of mucus obstruction in COPD. These findings prompted the search for CFTR potentiators that are more effective in ameliorating cigarette-smoke (CS) induced mucostasis. Methods: A novel small molecule potentiator (SK-POT1), previously identified in CFTR binding studies, was tested for its activity in augmenting CFTR channel activity using patch clamp electrophysiology in HEK-293 cells, a fluorescence-based assay of membrane potential in Calu-3 cells and in Ussing chamber studies of primary bronchial epithelial cultures. Addition of cigarette smoke extract (CSE) to the solutions bathing the apical surface of Calu-3 cells and primary bronchial airway cultures was used to model COPD. Confocal studies of the velocity of fluorescent microsphere movement on the apical surface of CSE exposed airway epithelial cultures, were used to assess the effect of potentiators on CFTR-mediated mucociliary movement. Results: We showed that SK-POT1, like VX-770, was effective in augmenting the cyclic AMP-dependent channel activity of CFTR. SK-POT-1 enhanced CFTR channel activity in airway epithelial cells previously exposed to CSE and ameliorated mucostasis on the surface of primary airway cultures. Conclusion: Together, this evidence supports the further development of SK-POT1 as an intervention in the treatment of COPD.
ABSTRACT
INTRODUCTION: Dentistry, being one of the healing professions, has an obligation to society that its members will stick on to high ethical standards of conduct. In India, studies done to assess whether the dental practitioners adhere to ethics in their line of work are very meager. AIM: The present study was conducted to assess the knowledge and practice of ethics in their line of work among practicing dentists from various dental colleges in Bangalore, India. MATERIALS AND METHODS: A descriptive cross-sectional survey was conducted among 258 practicing dentists attached to various dental colleges in Bangalore city of Karnataka, India. Independent sample t-test was used to compare the knowledge and practice scores according to gender and qualification. One way ANOVA was used to compare knowledge and practice score according to practice type and practice period. RESULTS: Mean knowledge score among males is 8.9 as compared to 9.43 among females and mean practice scores among males was 8.25 as compared to 8.29 in females. Statistically significant differences were found in the mean knowledge and practice scores among graduate dentists and specialists. Mean knowledge score among graduate dentists was 8.44 as compared to 9.36 among specialists and mean practice scores among graduate dentists was 7.7 as compared to 8.53 in specialists. CONCLUSION: A significant association between the knowledge and practice scores was observed, implying that with an increase in knowledge, there was also an increase in the practices of ethics among study population.
