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https://www.readbyqxmd.com/read/29025882/mucolytics-for-copd-negotiating-a-slippery-slope-towards-proof-of-efficacy
#1
EDITORIAL
Shawn D Aaron
No abstract text is available yet for this article.
October 2017: European Respiratory Journal: Official Journal of the European Society for Clinical Respiratory Physiology
https://www.readbyqxmd.com/read/28987048/-the-application-of-n-acetylcysteine-in-optimization-of-specific-pharmacological-therapies
#2
REVIEW
Iga Hołyńska-Iwan, Marcin Wróblewski, Dorota Olszewska-Słonina, Tomasz Tyrakowski
Based on the analysis of data from clinical trials it could be postulated that N-acetylcysteine has a positive impact on the treatment of various diseases. However, less is known about specific molecular and physiological mechanisms underlying the reported therapeutic effects. N-acetylcysteine (NAC, N-acetyl-L-cysteine) is an amino acid derivative containing a thiol group. It is a precursor of L-cysteine and glutathione. NAC is well absorbed and safe for the body at doses up to 300 mg per kg of body weight...
September 29, 2017: Polski Merkuriusz Lekarski: Organ Polskiego Towarzystwa Lekarskiego
https://www.readbyqxmd.com/read/28964880/chemical-modification-of-drug-molecules-as-strategy-to-reduce-interactions-with-mucus
#3
Francisca Araújo, Cláudia Martins, Cláudia Azevedo, Bruno Sarmento
Many drug molecules possess inadequate physical-chemical characteristics that prevent to surpass the viscous mucus layer present in the surface of mucosal tissues. Due to mucus protective role and its fast turnover, these drug molecules end up being removed from the body before being absorbed and, thus, before exerting any physiologic affect. Envisaging a better pharmacokinetics profile, chemical modifications, to render drug a more mucopenetrating character, have been introduced to drug molecules backbone towards more effective therapies...
September 27, 2017: Advanced Drug Delivery Reviews
https://www.readbyqxmd.com/read/28916389/removal-and-killing-of-multispecies-endodontic-biofilms-by-n-acetylcysteine
#4
Young-Suk Choi, Cheul Kim, Ji-Hoi Moon, Jin-Yong Lee
Removal of bacterial biofilm from the root canal system is essential for the management of endodontic disease. Here we evaluated the antibacterial effect of N-acetylcysteine (NAC), a potent antioxidant and mucolytic agent, against mature multispecies endodontic biofilms consisting of Actinomyces naeslundii, Lactobacillus salivarius, Streptococcus mutans and Enterococcus faecalis on sterile human dentin blocks. The biofilms were exposed to NAC (25, 50 and 100mg/mL), saturated calcium hydroxide or 2% chlorhexidine solution for 7 days, then examined by scanning electron microscopy...
September 2, 2017: Brazilian Journal of Microbiology: [publication of the Brazilian Society for Microbiology]
https://www.readbyqxmd.com/read/28915583/n-acetylcysteine-breaks-resistance-to-trastuzumab-caused-by-muc4-overexpression-in-human-her2-positive-bc-bearing-nude-mice-monitored-by-89-zr-trastuzumab-and-18-f-fdg-pet-imaging
#5
Zéna Wimana, Geraldine Gebhart, Thomas Guiot, Bruno Vanderlinden, Denis Larsimont, Gilles Doumont, Gaetan Van Simaeys, Serge Goldman, Patrick Flamen, Ghanem Ghanem
Trastuzumab remains an important drug in the management of human epidermal growth factor receptor 2 (HER2) overexpressing breast cancer (BC). Several studies reported resistance mechanisms to trastuzumab, including impaired HER2-accessibility caused by mucin 4 (MUC4). Previously, we demonstrated an increase of Zirconium-89-radiolabeled-trastuzumab ((89)Zr-Trastuzumab) accumulation when MUC4-overexpressing BC-cells were challenged with the mucolytic drug N-Acetylcysteine (NAC). Hereby, using the same approach we investigated whether tumor exposure to NAC would also enhance trastuzumab-efficacy...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28902888/dendrimer-based-selective-autophagy-induction-rescues-%C3%AE-f508-cftr-and-inhibits-pseudomonas-aeruginosa-infection-in-cystic-fibrosis
#6
Scott Mackenzie Brockman, Manish Bodas, David Silverberg, Ajit Sharma, Neeraj Vij
BACKGROUND: Cystic Fibrosis (CF) is a genetic disorder caused by mutation(s) in the CF-transmembrane conductance regulator (Cftr) gene. The most common mutation, ΔF508, leads to accumulation of defective-CFTR protein in aggresome-bodies. Additionally, Pseudomonas aeruginosa (Pa), a common CF pathogen, exacerbates obstructive CF lung pathology. In the present study, we aimed to develop and test a novel strategy to improve the bioavailability and potentially achieve targeted drug delivery of cysteamine, a potent autophagy-inducing drug with anti-bacterial properties, by developing a dendrimer (PAMAM-DEN)-based cysteamine analogue...
2017: PloS One
https://www.readbyqxmd.com/read/28889106/prevention-of-copd-exacerbations-a-european-respiratory-society-american-thoracic-society-guideline
#7
Jadwiga A Wedzicha, Peter M A Calverley, Richard K Albert, Antonio Anzueto, Gerard J Criner, John R Hurst, Marc Miravitlles, Alberto Papi, Klaus F Rabe, David Rigau, Pawel Sliwinski, Thomy Tonia, Jørgen Vestbo, Kevin C Wilson, Jerry A Krishnan
This document provides clinical recommendations for the prevention of chronic obstructive pulmonary disease (COPD) exacerbations. It represents a collaborative effort between the European Respiratory Society and the American Thoracic Society.Comprehensive evidence syntheses were performed to summarise all available evidence relevant to the Task Force's questions. The evidence was appraised using the Grading of Recommendations, Assessment, Development and Evaluation approach and the results were summarised in evidence profiles...
September 2017: European Respiratory Journal: Official Journal of the European Society for Clinical Respiratory Physiology
https://www.readbyqxmd.com/read/28874611/how-should-aerosols-be-delivered-during-invasive-mechanical-ventilation
#8
Rajiv Dhand
The delivery of aerosols to mechanically ventilated patients presents unique challenges and differs from inhaled drug delivery in spontaneously breathing patients in several respects. Successful aerosol delivery during invasive mechanical ventilation requires careful consideration of a host of factors that influence the amount of drug inhaled by the patient. Pressurized metered-dose inhalers and nebulizers (jet, ultrasonic, and vibrating mesh) are the most commonly used aerosol delivery devices in these patients, although other delivery devices, such as dry powder inhalers, soft mist inhalers, and intratracheal nebulizing catheters, could also be adapted for in-line use...
October 2017: Respiratory Care
https://www.readbyqxmd.com/read/28828368/inhalation-therapies-in-acute-respiratory-distress-syndrome
#9
REVIEW
Antonio Artigas, Marta Camprubí-Rimblas, Neus Tantinyà, Josep Bringué, Raquel Guillamat-Prats, Michael A Matthay
The defining features of acute respiratory distress syndrome (ARDS) are an excessive inflammatory respiratory response associated with high morbidity and mortality. Treatment consists mainly of measures to avoid worsening lung injury and cannot reverse the underlying pathophysiological process. New pharmacological agents have shown promising results in preclinical studies; however, they have not been successfully translated to patients with ARDS. The lack of effective therapeutic interventions has resulted in a recent interest in strategies to prevent ARDS with treatments delivering medications directly to the lungs by inhalation and nebulization, hopefully minimizing systemic adverse events...
July 2017: Annals of Translational Medicine
https://www.readbyqxmd.com/read/28783898/innovative-spe-lc-ms-ms-technique-for-the-assessment-of-63-pharmaceuticals-and-the-detection-of-antibiotic-resistant-bacteria-a-case-study-natural-water-sources-in-lebanon
#10
Samia Mokh, Mohammad El Khatib, Mohamad Koubar, Zeina Daher, Mohamad Al Iskandarani
A powerful analytical method for simultaneous determination of 63 pharmaceuticals and some metabolites in aqueous samples has been developed. The list of compounds amenable to the methods includes different therapeutic classes belonging to antibiotics, stimulants, antidepressants, mucolytics, and antiparasites. The method involves concentration and clean up by an offline solid phase extraction SPE followed by liquid chromatography coupled to tandem mass spectrometry (LC-ESI-MS/MS). The recovery of the target compounds from water samples was most efficient on Waters Oasis HLB SPE cartridge, while acetonitrile/water (60/40) was shown to be the most suitable solvent for desorbing the compounds from SPE...
December 31, 2017: Science of the Total Environment
https://www.readbyqxmd.com/read/28782582/development-and-in-vitro-characterization-of-a-papain-loaded-mucolytic-self-emulsifying-drug-delivery-system-sedds
#11
Christina Leichner, Claudia Menzel, Flavia Laffleur, Andreas Bernkop-Schnürch
The aim of the study was to create a self-emulsifying drug delivery system (SEDDS) with mucolytic properties based on incorporated papain for improved mucus permeation. In order to increase the lipophilicity of the enzyme and to dissolve it in SEDDS, hydrophobic ion pairing with sodium deoxycholate in a molar ratio of 20:1 (surfactant: enzyme) was performed. The yield of precipitated papain was 86.8±2.7% and the ion pair was loaded into the formulations to 1% (m/m). Suitable formulations were chosen according to their properties to dissolve the ion pair and characterized regarding droplet size and polydispersity index...
August 3, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/28769592/drug-induced-dyspnea-versus-cystic-fibrosis-exacerbation-a-diagnostic-dilemma
#12
Saqib Walayat, Nooreen Hussain, Jaymon Patel, Faiz Hussain, Preeti Patel, Sonu Dhillon, Bhagat Aulakh, Subramanyam Chittivelu
Cystic fibrosis (CF) is a disease caused by a mutation in the cystic fibrosis transmembrane conductance regulator protein in the epithelial membrane, and affects at least 30,000 people in the USA. There are between 900 and 1000 new cases diagnosed every year. Traditionally, CF has been treated symptomatically with pancreatic enzymes, bronchodilators, hypertonic saline, and pulmozyme. In July 2015, the US Food and Drug Administration approved Orkambi (lumacaftor/ivacaftor), a combination drug that works on reversing the effects of the defective cystic fibrosis transmembrane conductance regulator protein...
2017: International Medical Case Reports Journal
https://www.readbyqxmd.com/read/28753070/impact-of-mucolytic-agents-on-copd-exacerbations-a-pair-wise-and-network-meta-analysis
#13
Mario Cazzola, Paola Rogliani, Luigino Calzetta, Nicola A Hanania, Maria Gabriella Matera
Mucolytics are potentially useful for the management of chronic obstructive pulmonary disease (COPD), although there is conflicting advice on their use in different guideline documents. Furthermore, there is paucity of data comparing the efficacy of the different mucolytic agents in reducing the odds of COPD exacerbations. We performed pair-wise and network meta-analyses to evaluate the impact of mucoly-tics in COPD. Randomized clinical trials lasting at least 3 months and investigating the effects of mucolytics on COPD exacerbations were identified from published studies and repository databases...
October 2017: COPD
https://www.readbyqxmd.com/read/28748285/toward-the-standardization-of-mycological-examination-of-sputum-samples-in-cystic-fibrosis-results-from-a-french-multicenter-prospective-study
#14
Noémie Coron, Marc Pihet, Emilie Fréalle, Yolande Lemeille, Claudine Pinel, Hervé Pelloux, Gilles Gargala, Loic Favennec, Isabelle Accoceberry, Isabelle Durand-Joly, Frédéric Dalle, Frédéric Huet, Annlyse Fanton, Amale Boldron, Guy-André Loeuille, Philippe Domblides, Bérengère Coltey, Isabelle Pin, Catherine Llerena, Françoise Troussier, Christine Person, Christophe Marguet, Nathalie Wizla, Caroline Thumerelle, Dominique Turck, Stéphanie Bui, Michael Fayon, Alain Duhamel, Anne Prévotat, Benoit Wallaert, Sylvie Leroy, Jean-Philippe Bouchara, Laurence Delhaes
Fungal respiratory colonization of cystic fibrosis (CF) patients emerges as a new concern; however, the heterogeneity of mycological protocols limits investigations. We first aimed at setting up an efficient standardized protocol for mycological analysis of CF sputa that was assessed during a prospective, multicenter study: "MucoFong" program (PHRC-06/1902). Sputa from 243 CF patients from seven centers in France were collected over a 15-month period and submitted to a standardized protocol based on 6 semi-selective media...
July 26, 2017: Mycopathologia
https://www.readbyqxmd.com/read/28736302/beyond-pegylation-alternative-surface-modification-of-nanoparticles-with-mucus-inert-biomaterials
#15
Vitaliy V Khutoryanskiy
Mucus is a highly hydrated viscoelastic gel present on various moist surfaces in our body including the eyes, nasal cavity, mouth, gastrointestinal, respiratory and reproductive tracts. It serves as a very efficient barrier that prevents harmful particles, viruses and bacteria from entering the human body. However, the protective function of the mucus also hampers the diffusion of drugs and nanomedicines, which dramatically reduces their efficiency. Functionalisation of nanoparticles with low molecular weight poly(ethylene glycol) (PEGylation) is one of the strategies to enhance their penetration through mucus...
July 20, 2017: Advanced Drug Delivery Reviews
https://www.readbyqxmd.com/read/28730380/acute-and-chronic-effects-of-oral-erdosteine-on-ciliary-beat-frequency-cough-sensitivity-and-airway-reactivity
#16
L Pappová, I Kazimierová, M Jošková, M Šutovská, S Fraňová
Erdosteine as a mucolytic agent that decreases mucus viscosity and facilitates mucus expulsion from the airways by cough or ciliary movement. Our objective was to determine whether erdosteine can directly contribute to mucus clearance. We addressed the issue by monitoring acute and chronic effects of erdosteine on ciliary beat frequency (CBF), cough sensitivity, and airway smooth muscle reactivity. The experiments were performed in healthy guinea pigs. Erdosteine (10 mg/kg) was administrated orally in a single dose or daily through 7 days...
July 21, 2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28675773/a-polymer-chemistry-point-of-view-on-mucoadhesion-and-mucopenetration
#17
REVIEW
Philipp Schattling, Essi Taipaleenmäki, Yan Zhang, Brigitte Städler
Although oral is the preferred route of administration of pharmaceutical formulations, the long-standing challenge for medically active compounds to efficiently cross the mucus layer barrier limits its wider applicability. Efforts in nanomedicine to overcome this hurdle consider mucoadhesive and mucopenetrating drug carriers by selectively designing (macromolecular) building blocks. This review highlights and critically discusses recent strategies developed in this context including poly(ethylene glycol)-based modifications, cationic and thiolated polymers, as well as particles with high charge density, zeta-potential shifting ability, or mucolytic properties...
July 4, 2017: Macromolecular Bioscience
https://www.readbyqxmd.com/read/28658521/the-in-vitro-mucolytic-effect-of-xylitol-and-dornase-alfa-on-chronic-rhinosinusitis-mucus
#18
Tim Hardcastle, Ravi Jain, Fiona Radcliff, Sharon Waldvogel-Thurlow, Melissa Zoing, Kristi Biswas, Richard Douglas
BACKGROUND: The overproduction and stagnation of purulent mucus impair mucociliary clearance and exacerbate the symptoms of chronic rhinosinusitis (CRS). There is a clinical need for effective topical mucolytic agents to facilitate removal of mucus and improve postoperative outcomes. METHODS: The effects of xylitol (5%) and dornase alfa (1 mg/mL) on mucus and mucus crusts were investigated. Viscoelasticity and viscosity of wet mucus derived from 30 CRS patients was measured with a plate rheometer...
September 2017: International Forum of Allergy & Rhinology
https://www.readbyqxmd.com/read/28601320/protective-role-of-erdosteine-pretreatment-on-oleic-acid-induced-acute-lung-injury
#19
Ayşen Erdem, Esra Gedikli, Nilgün Yersal, Serkan Karaismailoglu, Sevda Muftuoglu, Ersin Fadillioglu, Meltem Tuncer
BACKGROUND: Erdosteine is a mucolytic agent with antioxidant and anti-inflammatory effects. We evaluated the protective effect of erdosteine pretreatment on oleic acid (OA)-induced acute lung injury. MATERIALS AND METHODS: Twenty-four male Wistar Albino rats were assigned to four treatments: control (oral saline + 50 μL intravenous [i.v.] saline), OA (oral saline + 50 μL i.v. OA), erdosteine (150 mg/kg oral erdosteine + 50 μL i.v. saline), and OA + erdosteine (150 mg/kg oral erdosteine + 50 μL i...
June 1, 2017: Journal of Surgical Research
https://www.readbyqxmd.com/read/28504001/n-acetylcysteine-potentiates-diclofenac-toxicity-in-saccharomyces-cerevisiae-stronger-potentiation-in-abc-transporter-mutant-strains
#20
Houssein Al-Attrache, Hala Chamieh, Monzer Hamzé, Isabelle Morel, Samir Taha, Ziad Abdel-Razzak
Diclofenac (DCF) adverse reactions involve diverse mechanisms in different models. We recently demonstrated that DCF-induced toxicity in HepaRG decreases as they express DCF-metabolizing enzymes. DCF metabolism promotes toxicity in Saccharomyces cerevisiae expressing heterologous cytochromes-P450. N-Acetylcysteine (NAC) is used to treat diverse medical conditions due to its multiple properties (antioxidant, metal chelator, thiol-disulfide disruption). The latter property accounts for its mucolytic effects and broadens its potential molecular targets to signal transduction proteins, ABC transporters and others...
May 15, 2017: Drug and Chemical Toxicology
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