Search results for "Cystic Fibrosis"
showing 10 items of 113 documents
Thymidine-dependent Staphylococcus aureus small-colony variants: human pathogens that are relevant not only in cases of cystic fibrosis lung disease.
2008
ABSTRACT We report the isolation of thymidine-dependent small-colony variants (TD-SCVs) of Staphylococcus aureus from unusual infection sites of patients with chronic soft tissue infection, tympanitis, bronchitis, peritonitis, and septicemia. Furthermore, we provide evidence that the essential growth factor for TD-SCVs, i.e., thymidine, and its metabolite dTMP are present in various human specimens.
Treatment of Pulmonary Disease of Cystic Fibrosis: A Comprehensive Review.
2021
Cystic fibrosis (CF) is a genetic disease that causes absence or dysfunction of a protein named transmembrane conductance regulatory protein (CFTR) that works as an anion channel. As a result, the secretions of the organs where CFTR is expressed are very viscous, so their functionality is altered. The main cause of morbidity is due to the involvement of the respiratory system as a result of recurrent respiratory infections by different pathogens. In recent decades, survival has been increasing, rising by around age 50. This is due to the monitoring of patients in multidisciplinary units, early diagnosis with neonatal screening, and advances in treatments. In this chapter, we will approach t…
Novel tricyclic pyrrolo-quinolines as pharmacological correctors of the mutant CFTR chloride channel
2023
AbstractF508del, the most frequent mutation in cystic fibrosis (CF), impairs the stability and folding of the CFTR chloride channel, thus resulting in intracellular retention and CFTR degradation. The F508del defect can be targeted with pharmacological correctors, such as VX-809 and VX-445, that stabilize CFTR and improve its trafficking to plasma membrane. Using a functional test to evaluate a panel of chemical compounds, we have identified tricyclic pyrrolo-quinolines as novel F508del correctors with high efficacy on primary airway epithelial cells from CF patients. The most effective compound, PP028, showed synergy when combined with VX-809 and VX-661 but not with VX-445. By testing the …
Staphylococcal Biofilms:Challenges in the Discovery of Novel Antiinfective Agents
2011
Staphylococci can induce a wide spectrum of infectious diseases that are associated with remarkable morbidity and mortality [1]. In fact, community and hospital-acquired methicillin resistant Staphylococcus aureus (MRSA) is a major health problem that has created a pressing need for novel therapeutic options [2]. Importantly, pathogenic staphylococci have not only an amazing ability to acquire resistance to antibiotics, but also to form biofilms, bacterial communities that grow on surfaces and are surrounded by a self-produced polymer matrix. This latter characteristic is likely the most important virulence factor of staphylococci in the development of the chronic form of infectious disease…
PO-0359 How To Select The Sweat Test Candidate. 10 Years Of Experience In Screening For Cystic Fibrosis In Children
2014
Background Sweat test (ST) remains gold standard in cystic fibrosis (CF) diagnosis. Alarm symptoms are age-related. Aims Retrospective review of cases subjected to ST. Methods Patients were selected by paediatricians, neonatologists, surgeons, based on suggestive symptoms, personal (PH) and familial history (FH). Inclusion criteria: for 0–1 month age group, patients with PH of atelectasis, meconium ileus, intussusception; 1–12 months, recurrent wheezing (RW), failure to thrive (FTT); 1–5 years, previous group symptoms, plus chronic cough/diarrhoea; >5 years, 1–5 years symptoms, plus recurrent pancreatitis/sinusitis. For all age, patients with PH of salty taste of sweat (STS), salt wasting s…
Nonsense codons suppression. An acute toxicity study of three optimized TRIDs in murine model, safety and tolerability evaluation.
2022
Stop mutations cause 11% of the genetic diseases, due to the introduction of a premature termination codon (PTC) in the mRNA, followed by the production of a truncated protein. A promising therapeutic approach is the suppression therapy by Translational Readthrough Inducing Drugs (TRIDs), restoring the expression of the protein. Recently, three new TRIDs (NV848, NV914, NV930) have been proposed, and validated by several in vitro assays, for the rescue of the CFTR protein, involved in Cystic Fibrosis disease. In this work, an acute toxicological study for the three TRIDs was conducted in vivo on mice, according to the OECD No.420 guidelines. Animals were divided into groups and treated with …
PEGYLATED POLYASPARTAMIDE–POLYLACTIDE BASED NANOPARTICLES PENETRATING CYSTIC FIBROSIS ARTIFICIAL MUCUS
2016
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. The high surface poly(ethylene gly…
An overview on chemical structures as ΔF508-CFTR correctors
2019
Deletion of phenylalanine at position 508 (F508del) in the CFTR protein, is the most common mutation causing cystic fibrosis (CF). F508del causes misfolding and rapid degradation of CFTR protein a defect that can be targeted with pharmacological agents termed “correctors”. Correctors belong to various chemical classes but are generally small molecules based on nitrogen sulfur or oxygen heterocycles. The mechanism of action of correctors is generally unknown but there is experimental evidence that some of them can directly act on mutant CFTR improving folding and stability. Here we overview the characteristics of the various F508del correctors described so far to obtain indications on key ch…
Polyanion–tobramycin nanocomplexes into functional microparticles for the treatment of Pseudomonas aeruginosa infections in cystic fibrosis
2016
Aim: Efficacy of antibiotics in cystic fibrosis (CF) is compromised by the poor penetration through mucus barrier. This work proposes a new ‘nano-into-micro’ approach, used to obtain a combinatorial effect: achieve a sustained delivery of tobramycin and overcome mucus barrier. Methods: Mannitol microparticles (MPs) were loaded with a tobramycin polymeric nanocomplex and characterized in presence of CF artificial mucus. Results & discussion: MPs are able to alter the rheological properties of CF artificial mucus, enhancing drug penetration into it and allowing a prolonged drug release. MPs resulted to be effective in Pseudomonas aeruginosa infections if compared with free tobramycin. Co…
Nanometric ion pair complexes of tobramycin forming microparticles for the treatment of Pseudomonas aeruginosa infections in cystic fibrosis
2019
Abstract Sustained pulmonary delivery of tobramycin from microparticles composed of drug/polymer nanocomplexes offers several advantages against traditional delivery methods. Namely, in patients with cystic fibrosis, microparticle delivery can protect the tobramycin being delivered from strong mucoadhesive interactions, thus avoiding effects on its diffusion toward the infection site. Polymeric ion-pair complexes were obtained starting from two synthetic polyanions, through impregnation of their solid dissociated forms with tobramycin in aqueous solution. The structure of these polymeric systems was characterized, and their activities were examined against various biofilm-forming Pseudomona…