Background:Mucociliary clearance is an important defense mechanism in human upper and lower respiratory airways.Impairment of this process by certain conditions such as cigarette smoking can predispose to chronic infe...Background:Mucociliary clearance is an important defense mechanism in human upper and lower respiratory airways.Impairment of this process by certain conditions such as cigarette smoking can predispose to chronic infection and neoplasm of the nose and paranasal sinuses.Methods:This was a cross-sectional study conducted in Kano metropolis,Nigeria.Eligible adults were enrolled,a saccharine test was conducted,and the nasal mucociliary clearance time was assessed.Analysis of the result was carried out using Statistical Product and Service Solutions version 23.0.Results:There were 225 participants categorized into 75 active smokers(33.3%),74 passive smokers(32.9%),and 76 nonsmokers(33.8%,living in a smoking-free zone).The age range of the participants was between 18 and 50 years,with a mean age of(31.2±5.6)years.All participants were males.There were 139(61.8%)of Hausa-Fulani ethnic group,24(10.7%)Yoruba,18(8.0%)Igbo,and 44(19.5%)other ethnic groups.Findings in this study showed that the average mucociliary clearance time among active smokers was prolonged([15.25±6.20]min)compared to passive([11.41±4.25]min)and nonsmokers([9.17±2.76]min)respectively,with a statistical significance(F=33.59,P<0.001).Binary logistic regression revealed that the number of cigarettes smoked per day was an independent predictor of prolonged mucociliary clearance time(P=0.008,odds ratio=0.44,95%confidence interval=0.24–0.80).Conclusion:Active cigarette smoking is associated with prolonged nasal mucociliary clearance time.The number of cigarette sticks smoked per day was found to be an independent predictor of prolonged mucociliary clearance time.展开更多
Objective:To focus on the asthmatic pathogenesis and clinical manifestations related to epithelial sodium channel (ENaC)/chlorine ion channel.Data Sources:The data analyzed in this review were the English articles...Objective:To focus on the asthmatic pathogenesis and clinical manifestations related to epithelial sodium channel (ENaC)/chlorine ion channel.Data Sources:The data analyzed in this review were the English articles from 1980 to 2015 from journal databases,primarily PubMed and Google Scholar.The terms used in the literature search were:(1) ENaCs;cystic fibrosis (CF) transmembrane conductance regulator (CFTR);asthma/asthmatic,(2) ENaC/sodium salt;CF;asthma/asthmatic,(3) CFTR/chlorine ion channels;asthma/asthmatic,(4) ENaC/sodium channel/scnn1a/scnn1b/scnn1g/scnn1d/amiloride-sensitive/amiloride-inhibtable sodium channels/sodium salt;asthma/asthmatic,lung/pulmonary/respiratory/tracheal/alveolar,and (5) CFTR;CF;asthma/asthmatic (ti).Study Selection:These studies included randomized controlled trials or studies covering asthma pathogenesis and clinical manifestations related to ENaC/chlorine ion channels within the last 25 years (from 1990 to 2015).The data involving chronic obstructive pulmonary disease and CF obtained from individual studies were also reviewed by the authors.Results:Airway surface liquid dehydration can cause airway inflammation and obstruction.ENaC and CFTR are closely related to the airway mucociliary clearance.Ion transporters may play a critical role in pathogenesis of asthmatic exacerbations.Conclusions:Ion channels have been the center of many studies aiming to understand asthmatic pathophysiological mechanisms or to identify therapeutic targets for better control of the disease.展开更多
Objective:Amphotericin B (AMB),a potent antifungal agent,has been employed as topical and systemic therapy for sinonasal fungal infections.A novel formulation of nanodisc (ND) containing super aggregated AMB (ND-AMB) ...Objective:Amphotericin B (AMB),a potent antifungal agent,has been employed as topical and systemic therapy for sinonasal fungal infections.A novel formulation of nanodisc (ND) containing super aggregated AMB (ND-AMB) for the treatment of fungal infections has been recently developed to provide greater protection from AMB toxicity than current,clinically approved lipid-based formulations.The objective of the current study was to evaluate the safety and potency of ND-AMB for sinonasal delivery using an in vitro model.Methods:Human sinonasal tissue was harvested during endoscopic sinus surgery and grown at air-liquid interface until well-differentiated.Cultures were exposed to ND-AMB vs AMB and changes in K+ permeability and resistance were measured and recorded via Ussing chamber assay.Ciliary beat frequency (CBF) was analyzed in parallel as well as cytotoxic assay.Potency was assessed using real-time PCR measurement of the Aspergillus fumigatus 18S rRNA.Results:Ussing chamber studies revealed K+ currents that increased rapidly within 30 s of adding AMB (10 μg/mL) to the apical side,indicating apical membranes had become permeable to K+ ions.In contrast,negligible induction of K+ current was obtained following addition of NDAMB [AMB =(107.7 ± 15.9) μA/cm2 AMB vs ND-AMB =(2.3 ± 0.7) μA/cm2 ND-AMB;P =0.005].ND-AMB also protected nasal epithelial cells from cytotoxicity of AMB (P < 0.05).There was no difference in ciliary beat frequency between the two groups (P =0.96).The expression of A.fumigatus 18S rRNA with exposure of lower dose of ND-AMB was significantly lower compared to that with AMB (P < 0.05).Conclusions:Data from the present study suggests ND-AMB protects human nasal epithelia membranes from AMB toxicity by protecting against apical cell K+ permeability while maintaining uncompromised antifungal property compared to AMB.ND-AMB could provide a novel topical therapy for sinonasal fungal diseases.展开更多
文摘Background:Mucociliary clearance is an important defense mechanism in human upper and lower respiratory airways.Impairment of this process by certain conditions such as cigarette smoking can predispose to chronic infection and neoplasm of the nose and paranasal sinuses.Methods:This was a cross-sectional study conducted in Kano metropolis,Nigeria.Eligible adults were enrolled,a saccharine test was conducted,and the nasal mucociliary clearance time was assessed.Analysis of the result was carried out using Statistical Product and Service Solutions version 23.0.Results:There were 225 participants categorized into 75 active smokers(33.3%),74 passive smokers(32.9%),and 76 nonsmokers(33.8%,living in a smoking-free zone).The age range of the participants was between 18 and 50 years,with a mean age of(31.2±5.6)years.All participants were males.There were 139(61.8%)of Hausa-Fulani ethnic group,24(10.7%)Yoruba,18(8.0%)Igbo,and 44(19.5%)other ethnic groups.Findings in this study showed that the average mucociliary clearance time among active smokers was prolonged([15.25±6.20]min)compared to passive([11.41±4.25]min)and nonsmokers([9.17±2.76]min)respectively,with a statistical significance(F=33.59,P<0.001).Binary logistic regression revealed that the number of cigarettes smoked per day was an independent predictor of prolonged mucociliary clearance time(P=0.008,odds ratio=0.44,95%confidence interval=0.24–0.80).Conclusion:Active cigarette smoking is associated with prolonged nasal mucociliary clearance time.The number of cigarette sticks smoked per day was found to be an independent predictor of prolonged mucociliary clearance time.
基金grants from American Heart Association grant (No. 20130034) and National Natural Science Foundation of China (No. 21307158).
文摘Objective:To focus on the asthmatic pathogenesis and clinical manifestations related to epithelial sodium channel (ENaC)/chlorine ion channel.Data Sources:The data analyzed in this review were the English articles from 1980 to 2015 from journal databases,primarily PubMed and Google Scholar.The terms used in the literature search were:(1) ENaCs;cystic fibrosis (CF) transmembrane conductance regulator (CFTR);asthma/asthmatic,(2) ENaC/sodium salt;CF;asthma/asthmatic,(3) CFTR/chlorine ion channels;asthma/asthmatic,(4) ENaC/sodium channel/scnn1a/scnn1b/scnn1g/scnn1d/amiloride-sensitive/amiloride-inhibtable sodium channels/sodium salt;asthma/asthmatic,lung/pulmonary/respiratory/tracheal/alveolar,and (5) CFTR;CF;asthma/asthmatic (ti).Study Selection:These studies included randomized controlled trials or studies covering asthma pathogenesis and clinical manifestations related to ENaC/chlorine ion channels within the last 25 years (from 1990 to 2015).The data involving chronic obstructive pulmonary disease and CF obtained from individual studies were also reviewed by the authors.Results:Airway surface liquid dehydration can cause airway inflammation and obstruction.ENaC and CFTR are closely related to the airway mucociliary clearance.Ion transporters may play a critical role in pathogenesis of asthmatic exacerbations.Conclusions:Ion channels have been the center of many studies aiming to understand asthmatic pathophysiological mechanisms or to identify therapeutic targets for better control of the disease.
文摘Objective:Amphotericin B (AMB),a potent antifungal agent,has been employed as topical and systemic therapy for sinonasal fungal infections.A novel formulation of nanodisc (ND) containing super aggregated AMB (ND-AMB) for the treatment of fungal infections has been recently developed to provide greater protection from AMB toxicity than current,clinically approved lipid-based formulations.The objective of the current study was to evaluate the safety and potency of ND-AMB for sinonasal delivery using an in vitro model.Methods:Human sinonasal tissue was harvested during endoscopic sinus surgery and grown at air-liquid interface until well-differentiated.Cultures were exposed to ND-AMB vs AMB and changes in K+ permeability and resistance were measured and recorded via Ussing chamber assay.Ciliary beat frequency (CBF) was analyzed in parallel as well as cytotoxic assay.Potency was assessed using real-time PCR measurement of the Aspergillus fumigatus 18S rRNA.Results:Ussing chamber studies revealed K+ currents that increased rapidly within 30 s of adding AMB (10 μg/mL) to the apical side,indicating apical membranes had become permeable to K+ ions.In contrast,negligible induction of K+ current was obtained following addition of NDAMB [AMB =(107.7 ± 15.9) μA/cm2 AMB vs ND-AMB =(2.3 ± 0.7) μA/cm2 ND-AMB;P =0.005].ND-AMB also protected nasal epithelial cells from cytotoxicity of AMB (P < 0.05).There was no difference in ciliary beat frequency between the two groups (P =0.96).The expression of A.fumigatus 18S rRNA with exposure of lower dose of ND-AMB was significantly lower compared to that with AMB (P < 0.05).Conclusions:Data from the present study suggests ND-AMB protects human nasal epithelia membranes from AMB toxicity by protecting against apical cell K+ permeability while maintaining uncompromised antifungal property compared to AMB.ND-AMB could provide a novel topical therapy for sinonasal fungal diseases.