Azithromycin and ciprofloxacin have a chloroquine-like effect on respiratory epithelial cells.

There is interest in the use of chloroquine/hydroxychloroquine (CQ/HCQ) and azithromycin (AZT) in COVID-19 therapy. Employing cystic fibrosis respiratory epithelial cells, here we show that drugs AZT and ciprofloxacin (CPX) act as acidotropic lipophilic weak bases and confer in vitro effects on intracellular organelles similar to the effects of CQ. These seemingly disparate FDA-approved antimicrobials display a common property of modulating pH of endosomes and trans-Golgi network.

Effect of treatment of cystic fibrosis pulmonary exacerbations on systemic inflammation.

Rationale: In cystic fibrosis (CF), pulmonary exacerbations present an opportunity to define the effect of antibiotic therapy on systemic measures of inflammation.

Objectives: Investigate whether plasma inflammatory proteins demonstrate and predict a clinical response to antibiotic therapy and determine which proteins are associated with measures of clinical improvement.

Methods: In this multicenter study, a panel of 15 plasma proteins was measured at the onset and end of treatment for pulmonary exacerbation and at a clinically stable visit in patients with CF who were 10 years of age or older.

Non-physician providers as clinical providers in cystic fibrosis: survey of U.S. programs.

Background And Methods: Non-physician providers (NPPs) including nurse practitioners (NPs) and physician assistants (PAs) are important members of CF care teams, but limited data exist about the extent NPPs are involved in CF care. A subcommittee was established by the CF Foundation to gather information about current involvement of NPPs. Surveys were sent to adult, pediatric and affiliate CF program directors (PDs) and NPPs working in US CF programs.

Elevated furin levels in human cystic fibrosis cells result in hypersusceptibility to exotoxin A-induced cytotoxicity.

Progressive pulmonary disease and infections with Pseudomonas aeruginosa remain an intractable problem in cystic fibrosis (CF). At the cellular level, CF is characterized by organellar hyperacidification, which results in altered protein and lipid glycosylation. Altered pH of the trans-Golgi network (TGN) may further disrupt the protein processing and packaging that occurs in this organelle.

Pharmacological modulation of cGMP levels by phosphodiesterase 5 inhibitors as a therapeutic strategy for treatment of respiratory pathology in cystic fibrosis.

The CFTR gene encodes a chloride channel with pleiotropic effects on cell physiology and metabolism. Here, we show that increasing cGMP levels to inhibit epithelial Na(+) channel in cystic fibrosis (CF) respiratory epithelial cells corrects several aspects of the downstream pathology in CF. Cell culture models, using a range of CF cell lines and primary cells, showed that complementary pharmacological approaches to increasing intracellular cGMP, by elevating guanyl cyclase activity though reduced nitric oxide, addition of cell-permeable cGMP analogs, or inhibition of phosphodiesterase 5 corrected multiple aspects of the CF pathological cascade.

Chloroquine normalizes aberrant transforming growth factor beta activity in cystic fibrosis bronchial epithelial cells.

Cystic fibrosis (CF) remains a fatal progressive disease in spite of the discovery and characterization of the CFTR gene. Transforming growth factor beta (TGF-beta) has been implicated in pathophysiology of CF. Previous reports have shown the trans-Golgi network (TGN) is hyperacdified in CF epithelial cells in culture and that this hyperacidification can be corrected with the membrane permeant weak base, chloroquine.

Endosomal hyperacidification in cystic fibrosis is due to defective nitric oxide-cylic GMP signalling cascade.

Endosomal hyperacidification in cystic fibrosis (CF) respiratory epithelial cells is secondary to a loss of sodium transport control owing to a defective form of the CF transmembrane conductance regulator CFTR. Here, we show that endosomal hyperacidification can be corrected by activating the signalling cascade controlling sodium channels through cyclic GMP. Nitric oxide (NO) donors corrected the endosomal hyperacidification in CF cells.

Perception of risk associated with asthma research procedures among adolescents, parents, and pediatricians.

Background: Little empirical data exist about how adolescents with asthma, their parents, and pediatricians view the risks and benefits associated with asthma clinical research.

Objective: Two studies examined similarities and differences in the perception of risks and benefits associated with asthma research.

Methods: In study I questionnaires were completed by adolescents with asthma and parents at the end of an audio and written presentation of a hypothetical research vignette.

Hyperacidification in cystic fibrosis: links with lung disease and new prospects for treatment.

A new link between the genetic defect and lung pathology in cystic fibrosis (CF) has been established by the recent discovery of an abnormally acidic pH in the organelles of CF respiratory epithelial cells, along with an increased acidity of the CF airway surface liquid. The defect in cystic fibrosis transmembrane resistance regulator (CFTR) results in hyperacidification of the trans-Golgi network, an organelle responsible for glycosylation, and protein- and membrane-sorting in mammalian cells. Hyperacidification and altered surface glycoconjugates might contribute to mucus thickening, bacterial adhesion and colonization, inflammation, and irreversible tissue damage.

VEGF regulates remodeling during permanent anatomic closure of the ductus arteriosus.

Anatomic remodeling and permanent closure of the newborn ductus arteriosus appears to require the development of intense hypoxia within the constricted vessel wall. Hypoxic ductus smooth muscle cells express vascular endothelial cell growth factor (VEGF). We studied premature baboons and sheep to determine the effects of VEGF inhibition (in baboons) and VEGF stimulation (in sheep) on ductus remodeling in vivo.