keyword
https://read.qxmd.com/read/27317686/ibuprofen-regulation-of-microtubule-dynamics-in-cystic-fibrosis-epithelial-cells
#21
JOURNAL ARTICLE
Sharon M Rymut, Claire M Kampman, Deborah A Corey, Tori Endres, Calvin U Cotton, Thomas J Kelley
High-dose ibuprofen, an effective anti-inflammatory therapy for the treatment of cystic fibrosis (CF), has been shown to preserve lung function in a pediatric population. Despite its efficacy, few patients receive ibuprofen treatment due to potential renal and gastrointestinal toxicity. The mechanism of ibuprofen efficacy is also unclear. We have previously demonstrated that CF microtubules are slower to reform after depolymerization compared with respective wild-type controls. Slower microtubule dynamics in CF cells are responsible for impaired intracellular transport and are related to inflammatory signaling...
August 1, 2016: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://read.qxmd.com/read/27055154/oral-non-steroidal-anti-inflammatory-drug-therapy-for-lung-disease-in-cystic-fibrosis
#22
REVIEW
Larry C Lands, Sanja Stanojevic
BACKGROUND: Progressive lung damage causes most deaths in cystic fibrosis. Non-steroidal anti-inflammatory drugs (such as ibuprofen) may prevent progressive pulmonary deterioration and morbidity in cystic fibrosis. OBJECTIVES: To assess the effectiveness of treatment with non-steroidal anti-inflammatory drugs in cystic fibrosis. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register comprising references identified from comprehensive electronic database searches, hand searches of relevant journals and abstract books of conference proceedings...
April 7, 2016: Cochrane Database of Systematic Reviews
https://read.qxmd.com/read/26894321/new-use-for-an-old-drug-cox-independent-anti-inflammatory-effects-of-sulindac-in-models-of-cystic-fibrosis
#23
JOURNAL ARTICLE
Jérémy Rocca, Sylvie Manin, Anne Hulin, Abdel Aissat, Wilfried Verbecq-Morlot, Virginie Prulière-Escabasse, Adeline Wohlhuter-Haddad, Ralph Epaud, Pascale Fanen, Agathe Tarze
BACKGROUND AND PURPOSE: Pulmonary disease is the main cause of morbidity and mortality in cystic fibrosis (CF) patients due to exacerbated inflammation. To date, the only anti-inflammatory drug available to CF patients is high-dose ibuprofen, which can slow pulmonary disease progression, but whose cyclooxygenase-dependent digestive adverse effects limit its clinical use. Here we have tested sulindac, another non-steroidal anti-inflammatory drug with an undefined anti-inflammatory effect in CF airway epithelial cells...
June 2016: British Journal of Pharmacology
https://read.qxmd.com/read/26866983/pegylated-polyaspartamide-polylactide-based-nanoparticles-penetrating-cystic-fibrosis-artificial-mucus
#24
JOURNAL ARTICLE
Emanuela Fabiola Craparo, Barbara Porsio, Carla Sardo, Gaetano Giammona, Gennara Cavallaro
Here, the preparation of mucus-penetrating nanoparticles for pulmonary administration of ibuprofen in patients with cystic fibrosis is described. A fluorescent derivative of α,β-poly(N-2-hydroxyethyl)-D,L-aspartamide is synthesized by derivatization with rhodamine, polylactide, and poly(ethylene glycol), to obtain polyaspartamide-polylactide derivatives with different degrees of pegylation. Starting from these copolymers, fluorescent nanoparticles with different poly(ethylene glycol) content, empty and loaded with ibuprofen, showed spherical shape, colloidal size, slightly negative ζ potential, and biocompatibility toward human bronchial epithelial cells...
March 14, 2016: Biomacromolecules
https://read.qxmd.com/read/25869324/use-of-ibuprofen-to-assess-inflammatory-biomarkers-in-induced-sputum-implications-for-clinical-trials-in-cystic-fibrosis
#25
RANDOMIZED CONTROLLED TRIAL
James F Chmiel, Michael W Konstan, Frank J Accurso, James Lymp, Nicole Mayer-Hamblett, Donald R VanDevanter, Lynn M Rose, Bonnie W Ramsey
BACKGROUND: High-dose ibuprofen (HDI) is a clinically beneficial anti-inflammatory regimen that may be a useful reagent to study induced sputum inflammatory marker changes over short study periods appropriate for early-phase CF clinical trials. METHODS: We conducted a 28-day, open-label, randomized, controlled trial among 72 clinically stable CF subjects (FEV1≥40% predicted) randomized to HDI or routine care that assessed IL-6, IL-8, TNF-α, IL-1-β, free neutrophil elastase, and white cell counts with differentials change from baseline in induced sputum...
November 2015: Journal of Cystic Fibrosis: Official Journal of the European Cystic Fibrosis Society
https://read.qxmd.com/read/25754096/treatment-and-demographic-factors-affecting-time-to-next-pulmonary-exacerbation-in-cystic-fibrosis
#26
JOURNAL ARTICLE
Donald R VanDevanter, David J Pasta, Michael W Konstan
BACKGROUND: Pulmonary exacerbations (PEx) are important CF clinical events. METHODS: We studied time to next PEx following intravenous (IV) antibiotic PEx treatment among Cleveland Ohio CF center patients occurring between January 2010 and September 2014. Patient demographics, clinical presentations, and treatments were modeled by Cox proportional hazards regression to identify covariates associated with time to next PEx. RESULTS: 193 patients were treated for PEx; 155 had a subsequent IV-treated PEx...
November 2015: Journal of Cystic Fibrosis: Official Journal of the European Cystic Fibrosis Society
https://read.qxmd.com/read/25707701/drug-drug-plasma-protein-binding-interactions-of-ivacaftor
#27
JOURNAL ARTICLE
Elena K Schneider, Johnny X Huang, Vincenzo Carbone, Mark Baker, Mohammad A K Azad, Matthew A Cooper, Jian Li, Tony Velkov
Ivacaftor is a novel cystic fibrosis (CF) transmembrane conductance regulator (CFTR) potentiator that improves the pulmonary function for patients with CF bearing a G551D CFTR-protein mutation. Because ivacaftor is highly bound (>97%) to plasma proteins, there is the strong possibility that co-administered CF drugs may compete for the same plasma protein binding sites and impact the free drug concentration. This, in turn, could lead to drastic changes in the in vivo efficacy of ivacaftor and therapeutic outcomes...
June 2015: Journal of Molecular Recognition: JMR
https://read.qxmd.com/read/24974227/ibuprofen-rescues-mutant-cystic-fibrosis-transmembrane-conductance-regulator-trafficking
#28
JOURNAL ARTICLE
Graeme W Carlile, Renaud Robert, Julie Goepp, Elizabeth Matthes, Jie Liao, Bart Kus, Sean D Macknight, Daniela Rotin, John W Hanrahan, David Y Thomas
BACKGROUND: Small molecules as shown by VX809 can rescue the mislocalization of F508del-CFTR. The aim of this study was to identify correctors with a clinical history and their targets of action. METHODS: CFTR correctors were screened using two F508del-CFTR expressing cell based HTS assays. Electrophysiological studies using CFBE41o(-) and HBE cells and in-vivo mouse assays confirmed CFTR rescue. The target of action was attained using pharmacological inhibitors and siRNA to specific genes...
January 2015: Journal of Cystic Fibrosis: Official Journal of the European Cystic Fibrosis Society
https://read.qxmd.com/read/24338982/medical-management-of-chronic-rhinosinusitis-in-cystic-fibrosis-a-systematic-review
#29
REVIEW
Jonathan Liang, Thomas Higgins, Stacey L Ishman, Emily F Boss, James R Benke, Sandra Y Lin
OBJECTIVES/HYPOTHESIS: To systematically review existing literature on the effectiveness of medical management of chronic rhinosinusitis (CRS) in cystic fibrosis (CF) patients. STUDY DESIGN: Systematic review. METHODS: We performed a literature search of PubMed, Embase, and Cochrane CENTRAL from 1987 to 2012. Inclusion criteria included English language as containing original data, with five or more subjects, measurable clinical outcomes, and readily available interventions...
June 2014: Laryngoscope
https://read.qxmd.com/read/23880054/antibiotic-and-anti-inflammatory-therapies-for-cystic-fibrosis
#30
REVIEW
James F Chmiel, Michael W Konstan, J Stuart Elborn
Cystic fibrosis (CF) lung disease is characterized by chronic bacterial infection and an unremitting inflammatory response, which are responsible for most of CF morbidity and mortality. The median expected survival has increased from <6 mo in 1940 to >38 yr now. This dramatic improvement, although not great enough, is due to the development of therapies directed at secondary disease pathologies, especially antibiotics. The importance of developing treatments directed against the vigorous inflammatory response was realized in the 1990s...
October 2013: Cold Spring Harbor Perspectives in Medicine
https://read.qxmd.com/read/23765216/oral-non-steroidal-anti-inflammatory-drug-therapy-for-lung-disease-in-cystic-fibrosis
#31
REVIEW
Larry C Lands, Sanja Stanojevic
BACKGROUND: Progressive lung damage causes most deaths in cystic fibrosis (CF). Non-steroidal anti-inflammatory drugs (NSAIDs) may prevent progressive pulmonary deterioration and morbidity in CF. OBJECTIVES: To assess the effectiveness of treatment with NSAIDs in CF. SEARCH METHODS: We searched the Cochrane CF and Genetic Disorders Group Trials Register comprising references identified from comprehensive electronic database searches, hand searches of relevant journals and abstract books of conference proceedings...
2013: Cochrane Database of Systematic Reviews
https://read.qxmd.com/read/23532925/high-dose-ibuprofen-is-not-associated-with-increased-biomarkers-of-kidney-injury-in-patients-with-cystic-fibrosis
#32
JOURNAL ARTICLE
Thomas Lahiri, Alyson Guillet, Sandra Diehl, Michael Ferguson
High-dose ibuprofen (IBU) may slow the decline of lung function in patients with cystic fibrosis (CF), but its use has been limited due to concerns over renal and gastrointestinal toxicity. In this pilot study, we examined the association of IBU with markers of acute kidney injury (AKI) in patients with CF. The effect of aminoglycoside (AG) exposure on AKI biomarkers was also examined. The AKI markers, kidney injury molecule-1 (KIM), N-acetyl-β-glucosaminidase (NAG) and urine protein, normalized for creatinine, were chosen as they are more sensitive indicators of kidney injury than changes in serum creatinine...
February 2014: Pediatric Pulmonology
https://read.qxmd.com/read/22174294/linking-pharmgkb-to-phenotype-studies-and-animal-models-of-disease-for-drug-repurposing
#33
JOURNAL ARTICLE
Robert Hoehndorf, Anika Oellrich, Dietrich Rebholz-Schuhmann, Paul N Schofield, Georgios V Gkoutos
The investigation of phenotypes in model organisms has the potential to reveal the molecular mechanisms underlying disease. The large-scale comparative analysis of phenotypes across species can reveal novel associations between genotypes and diseases. We use the PhenomeNET network of phenotypic similarity to suggest genotype-disease association, combine them with drug-gene associations available from the PharmGKB database, and infer novel associations between drugs and diseases. We evaluate and quantify our results based on our method's capability to reproduce known drug-disease associations...
2012: Pacific Symposium on Biocomputing
https://read.qxmd.com/read/21500868/targeting-airway-inflammation-in-cystic-fibrosis-in-children-past-present-and-future
#34
REVIEW
Tacjana Pressler
Inflammation is a major component of the vicious cycle characterizing cystic fibrosis (CF) pulmonary disease. If untreated, this inflammatory process irreversibly damages the airways, leading to bronchiectasis and ultimately respiratory failure. Anti-inflammatory drugs for CF lung disease appear to have beneficial effects on disease progression. These agents include oral corticosteroids and ibuprofen, as well as azithromycin, which, in addition to its antimicrobial effects, also possess anti-inflammatory properties...
June 1, 2011: Paediatric Drugs
https://read.qxmd.com/read/21454676/down-regulation-of-cytokine-induced-interleukin-8-requires-inhibition-of-p38-mitogen-activated-protein-kinase-mapk-via-mapk-phosphatase-1-dependent-and-independent-mechanisms
#35
JOURNAL ARTICLE
Nurlan Dauletbaev, Daniel Eklove, Nadir Mawji, Michele Iskandar, Sergio Di Marco, Imed-Eddine Gallouzi, Larry C Lands
Down-regulation of overabundant interleukin (IL)-8 present in cystic fibrosis (CF) airways could ease excessive neutrophil burden and its deleterious consequences for the lung. IL-8 production in airway epithelial cells, stimulated with e.g. inflammatory cytokines IL-1β and tumor necrosis factor (TNF)-α, is regulated by several signaling pathways including nuclear factor (NF)-κB and p38 mitogen-activated protein kinase (MAPK). We previously demonstrated that the anti-inflammatory drugs dexamethasone and ibuprofen suppress NF-κB; however, only dexamethasone down-regulates cytokine-induced IL-8, highlighting the importance of non-NF-κB mechanisms...
May 6, 2011: Journal of Biological Chemistry
https://read.qxmd.com/read/20717935/trends-in-the-use-of-routine-therapies-in-cystic-fibrosis-1995-2005
#36
MULTICENTER STUDY
Michael W Konstan, Donald R VanDevanter, Lawrence Rasouliyan, David J Pasta, Ashley Yegin, Wayne J Morgan, Jeffrey S Wagener
Many therapies are used to treat manifestations of cystic fibrosis (CF). Trends in routine therapy use in Epidemiologic Study of Cystic Fibrosis patients were studied from 1995 to 2005. Patients (15,087) were assessed in 1995; 12,778 in 2005. Observed differences in therapy use of ≥2% were statistically significant at P < 0.001. Comparing the 1995 and 2005 populations, mean age was 13.9 versus 15.5 years; weight-for-age percentile was 30.3 versus 36.9; and mean forced expiratory volume in 1 sec (FEV(1)) was 73...
December 2010: Pediatric Pulmonology
https://read.qxmd.com/read/19955700/targeting-inflammation-in-cystic-fibrosis
#37
EDITORIAL
Elisabeth Kieninger, Nicolas Regamey
No abstract text is available yet for this article.
2010: Respiration; International Review of Thoracic Diseases
https://read.qxmd.com/read/19887769/ibuprofen-modulates-nf-kb-activity-but-not-il-8-production-in-cystic-fibrosis-respiratory-epithelial-cells
#38
JOURNAL ARTICLE
Nurlan Dauletbaev, Joyce Lam, Daniel Eklove, Michele Iskandar, Larry C Lands
BACKGROUND: High-dose ibuprofen is clinically effective in cystic fibrosis (CF); however, its molecular mechanisms are poorly understood. OBJECTIVE: To test the hypothesis that clinically relevant concentrations of ibuprofen suppress activation of nuclear factor (NF)-kappaB and thus down-regulate stimulated interleukin (IL)-8 production in CF respiratory epithelial cells. METHODS: The majority of experiments were conducted in CFTE29o- cells (F508del-mutated CF transmembrane regulator, CFTR)...
2010: Respiration; International Review of Thoracic Diseases
https://read.qxmd.com/read/18812834/ibuprofen-therapy-for-cystic-fibrosis-lung-disease-revisited
#39
REVIEW
Michael W Konstan
PURPOSE OF REVIEW: Ibuprofen was first advocated as a chronic therapy for cystic fibrosis lung disease in 1995, following a favorable report of a 4-year controlled trial. However, clinical use has been limited primarily by the concern about adverse effects. Additional clinical studies were advocated to better assess the risk-benefit profile. The results of several studies have been published within the last couple of years. RECENT FINDINGS: Results from a 2-year multicenter trial were consistent with the 4-year trial in demonstrating a beneficial effect of ibuprofen on lung function in children with mild to moderate lung disease...
November 2008: Current Opinion in Pulmonary Medicine
https://read.qxmd.com/read/18760805/relationship-between-inhaled-corticosteroid-therapy-and-rate-of-lung-function-decline-in-children-with-cystic-fibrosis
#40
JOURNAL ARTICLE
Clement L Ren, David J Pasta, Lawrence Rasouliyan, Jeffrey S Wagener, Michael W Konstan, Wayne J Morgan et al.
OBJECTIVE: To assess the relationship between inhaled corticosteroids (ICS) use and lung function decline in children with cystic fibrosis (CF) using the Epidemiologic Study of Cystic Fibrosis, an observational study of patients with CF in North America. STUDY DESIGN: We analyzed data from 2978 patients 6 to 17 years old enrolled in ESCF between 1994 to 2004. We estimated the rate of decline in forced expiratory volume in 1 second (FEV(1)) before and after starting ICS therapy with a piecewise linear continuous single change point model, adjusting for potentially confounding covariates...
December 2008: Journal of Pediatrics
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