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  1 / 2049 MEDLINE  
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PMID:27860477
Author:Mlcáková E; Mlcák P; Karhanová M; Langová K; Maresová K
Title:Hodnocení ocního povrchu u pacientu lécených analogy prostaglandinu s ohledem na obsazenou konzervacní látku. [Ocular Surface Evaluation in Patients Treated with Prostaglandin Analogues Considering Preservative Agent].
Source:Cesk Slov Oftalmol; 72(4):120-127, 2016.
ISSN:1211-9059
Country of publication:Czech Republic
Language:cze
Abstract:PURPOSE: The aim of this study was to evaluate the ocular surface in patients treated with prostaglandin analogues considering contained preservative agent. METHODS: 60 patients with glaucoma or ocular hypertension treated with prostaglandin analogue monotherapy were enrolled in this observational study. 20 patients with glaucoma suspect or ocular hypertension without local or systemic glaucoma medication formed the control group. Demographic data and medical history were recorded for each participant. Patients filled in the Ocular surface disease index© (OSDI) questionnaire and underwent an ophthalmological examination including assessment of conjunctival hyperaemia according to Efron, tear film break up time (BUT) and fluorescein staining according to the Oxford grading scheme. Treated participants were divided into 3 groups according to the preservative contained in the currently used prostaglandin analogue: the preservative-free group (18 patients), the polyquaternium group (17 patients) and the benzalkonium chloride (BAK) group (25 patients). RESULTS: The control group had significantly lower fluorescein staining than the preservative-free group (p=0.001), the polyquaternium group (p=0.007) and the BAK group (p=0.002). The conjunctival hyperaemia was significantly lower in the preservative-free group compared to the polyquaternium group (p=0.011). There was no significant difference among the other groups. The difference neither in the OSDI score nor in the BUT was statistically important. CONCLUSION: This study confirmed that the ocular surface is worse in patients treated with prostaglandin analogue monotherapy than in people without glaucoma medication. A significant difference among treated patients depending on a preservative agent was not proved.Key words: benzalkonium chloride, glaucoma, ocular surface disease, preservatives, prostaglandin analogues.
Publication type:COMPARATIVE STUDY; JOURNAL ARTICLE
Name of substance:0 (Antihypertensive Agents); 0 (Benzalkonium Compounds); 0 (Ophthalmic Solutions); 0 (Polymers); 0 (Preservatives, Pharmaceutical); 0 (Prostaglandins F, Synthetic); 75345-27-6 (polyquaternium 1)


  2 / 2049 MEDLINE  
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PMID:28851528
Author:Slimani K; Féret A; Pirotais Y; Maris P; Abjean JP; Hurtaud-Pessel D
Address:ANSES, French Agency for Food, Environmental and Occupational Health & Safety, Fougères Laboratory, Residues and Contaminants Analysis Unit, France.
Title:Liquid chromatography-tandem mass spectrometry multiresidue method for the analysis of quaternary ammonium compounds in cheese and milk products: Development and validation using the total error approach.
Source:J Chromatogr A; 1517:86-96, 2017 Sep 29.
ISSN:1873-3778
Country of publication:Netherlands
Language:eng
Abstract:Quaternary ammonium compounds (QACs) are both cationic surfactants and biocidal substances widely used as disinfectants in the food industry. A sensitive and reliable method for the analysis of benzalkonium chlorides (BACs) and dialkyldimethylammonium chlorides (DDACs) has been developed that enables the simultaneous quantitative determination of ten quaternary ammonium residues in dairy products below the provisional maximum residue level (MRL), set at 0.1mgkg . To the best of our knowledge, this method could be the one applicable to milk and to three major processed milk products selected, namely processed or hard pressed cheeses, and whole milk powder. The method comprises solvent extraction using a mixture of acetonitrile and ethyl acetate, without any further clean-up. Analyses were performed by liquid chromatography coupled with electrospray tandem mass spectrometry detection (LC-ESI-MS/MS) operating in positive mode. A C18 analytical column was used for chromatographic separation, with a mobile phase composed of acetonitrile and water both containing 0.3% formic acid; and methanol in the gradient mode. Five deuterated internal standards were added to obtain the most accurate quantification. Extraction recoveries were satisfactory and no matrix effects were observed. The method was validated using the total error approach in accordance with the NF V03-110 standard in order to characterize the trueness, repeatability, intermediate precision and analytical limits within the range of 5-150µgkg for all matrices. These performance criteria, calculated by e.noval 3.0 software, were satisfactory and in full accordance with the proposed provisional MRL and with the recommendations in the European Union SANTE/11945/2015 regulatory guidelines. The limit of detection (LOD) was low (<1.9µgkg ) and the limit of quantification (LOQ) ranged from 5µgkg to 35µgkg for all matrices depending on the analytes. The validation results proved that the method is suitable for quantifying quaternary ammoniums in foodstuffs from dairy industries at residue levels, and could be used for biocide residues monitoring plans and to measure the exposition consumer to biocides products.
Publication type:JOURNAL ARTICLE; VALIDATION STUDIES
Name of substance:0 (Acetonitriles); 0 (Benzalkonium Compounds); 0 (Quaternary Ammonium Compounds); Z072SB282N (acetonitrile)


  3 / 2049 MEDLINE  
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PMID:28648294
Author:Rodríguez-López P; Cabo ML
Address:Department of Microbiology and Technology of Marine Products, Instituto de Investigaciones Marinas (IIM-CSIC), Eduardo Cabello 6, 36208 Vigo, Pontevedra, Spain.
Title:Tolerance development in Listeria monocytogenes-Escherichia coli dual-species biofilms after sublethal exposures to pronase-benzalkonium chloride combined treatments.
Source:Food Microbiol; 67:58-66, 2017 Oct.
ISSN:1095-9998
Country of publication:England
Language:eng
Abstract:This study was designed to assess the effects that sublethal exposures to pronase (PRN) and benzalkonium chloride (BAC) combined treatments have on Listeria monocytogenes-Escherichia coli dual-species biofilms grown on stainless steel in terms of tolerance development (TD) to these compounds. Additionally, fluorescence microscopy was used to observe the changes of the biofilm structure. PRN-BAC exposure was carried out using three different approaches and TD was evaluated treating biofilms with a final 100 µg/ml PRN followed by 50 µg/ml BAC combined treatment. Results showed that exposure to PRN-BAC significantly decreased the number of adhered L. monocytogenes (P < 0.05), while E. coli counts remained generally unaltered. It was also demonstrated that the incorporation of recovery periods during sublethal exposures increased the tolerance of both species of the mixed biofilm to the final PRN-BAC treatment. Moreover, control biofilms became more resistant to PRN-BAC if longer incubation periods were used. Regardless of the treatment used, log reduction values were generally lower in L. monocytogenes compared to E. coli. Additionally, microscopy images showed an altered morphology produced by sublethal PRN-BAC in exposed L. monocytogenes-E. coli dual-species biofilms compared to control samples. Results also demonstrated that L. monocytogenes-E. coli dual-species biofilms are able to develop tolerance to PRN-BAC combined treatments depending on way they have been previously exposed. Moreover, they suggest that the generation of bacterial tolerance should be included as a parameter for sanitation procedures design.
Publication type:JOURNAL ARTICLE
Name of substance:0 (Anti-Bacterial Agents); 0 (Benzalkonium Compounds); EC 3.4.24.- (Pronase)


  4 / 2049 MEDLINE  
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PMID:28581826
Author:Safwat MA; Soliman GM; Sayed D; Attia MA
Address:a Department of Pharmaceutics, Faculty of Pharmacy , Assiut University , Assiut , Egypt.
Title:Gold nanoparticles capped with benzalkonium chloride and poly (ethylene imine) for enhanced loading and skin permeability of 5-fluorouracil.
Source:Drug Dev Ind Pharm; 43(11):1780-1791, 2017 Nov.
ISSN:1520-5762
Country of publication:England
Language:eng
Abstract:OBJECTIVE: To enhance 5-fluorouracil (5-FU) permeability through the skin by loading onto gold nanoparticles (GNPs) capped with two cationic ligands, benzalkonium chloride (BC) or poly (ethylene imine) (PEI). Whereas 5-FU has excellent efficacy against many cancers, its poor permeability through biological membranes and several adverse effects limit its clinical benefits. BC and PEI were selected to stabilize GNPs and to load 5-FU through ionic interactions. METHODS: 5-FU/BC-GNPs and 5-FU/PEI-GNPs were prepared at different 5-FU/ligand molar ratios and different pH values and were evaluated using different techniques. GNPs stability was tested as a function of salt concentration and storage time. 5-FU release from BC- and PEI-GNPs was evaluated as a function of solution pH. Ex vivo permeability studies of different 5-FU preparations were carried out using mice skin. RESULTS: 5-FU-loaded GNPs size and surface charge were dependent on the 5-FU/ligand molar ratios. 5-FU entrapment efficiency and loading capacity were dependent on the used ligand, 5-FU/ligand molar ratio and solution pH. Maximum drug entrapment efficiency of 59.0 ± 1.7% and 46.0 ± 1.1% were obtained for 5-FU/BC-GNPs and 5-FU/PEI-GNPs, respectively. 5-FU-loaded GNPs had good stability against salinity and after storage for 4 months at room temperature and at 4 °C. In vitro 5-FU release was pH- and ligand-dependent where slower release was observed at higher pH and for 5-FU/BC-GNPs. 5-FU permeability through mice skin was significantly higher for drug-loaded GNPs compared with drug-ligand complex or drug aqueous solution. CONCLUSION: Based on these results, BC- and PEI-GNPs might find applications as effective topical delivery systems of 5-FU.
Publication type:JOURNAL ARTICLE
Name of substance:0 (Benzalkonium Compounds); 0 (Drug Carriers); 0 (Imines); 0 (Polyethylenes); 0 (poly(ethylene imine)); 7440-57-5 (Gold); U3P01618RT (Fluorouracil)


  5 / 2049 MEDLINE  
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PMID:28444329
Author:Datta S; Baudouin C; Brignole-Baudouin F; Denoyer A; Cortopassi GA
Address:Department of Molecular Bioscience, School of Veterinary Medicine, University of California, Davis, Davis, California, United States.
Title:The Eye Drop Preservative Benzalkonium Chloride Potently Induces Mitochondrial Dysfunction and Preferentially Affects LHON Mutant Cells.
Source:Invest Ophthalmol Vis Sci; 58(4):2406-2412, 2017 Apr 01.
ISSN:1552-5783
Country of publication:United States
Language:eng
Abstract:Purpose: Benzalkonium chloride (BAK) is the most commonly used eye drop preservative. Benzalkonium chloride has been associated with toxic effects such as "dry eye" and trabecular meshwork degeneration, but the underlying biochemical mechanism of ocular toxicity by BAK is unclear. In this study, we propose a mechanistic basis for BAK's adverse effects. Method: Mitochondrial O2 consumption rates of human corneal epithelial primary cells (HCEP), osteosarcoma cybrid cells carrying healthy (control) or Leber hereditary optic neuropathy (LHON) mutant mtDNA [11778(G>A)], were measured before and after acute treatment with BAK. Mitochondrial adenosine triphosphate (ATP) synthesis and cell viability were also measured in the BAK-treated control: LHON mutant and human-derived trabecular meshwork cells (HTM3). Results: Benzalkonium chloride inhibited mitochondrial ATP (IC50, 5.3 µM) and O2 consumption (IC50, 10.9 µM) in a concentration-dependent manner, by directly targeting mitochondrial complex I. At its pharmaceutical concentrations (107-667 µM), BAK inhibited mitochondrial function >90%. In addition, BAK elicited concentration-dependent cytotoxicity to cybrid cells (IC50, 22.8 µM) and induced apoptosis in HTM3 cells at similar concentrations. Furthermore, we show that BAK directly inhibits mitochondrial O2 consumption in HCEP cells (IC50, 3.8 µM) at 50-fold lower concentrations than used in eye drops, and that cells bearing mitochondrial blindness (LHON) mutations are further sensitized to BAK's mitotoxic effect. Conclusions: Benzalkonium chloride inhibits mitochondria of human corneal epithelial cells and cells bearing LHON mutations at pharmacologically relevant concentrations, and we suggest this is the basis of BAK's ocular toxicity. Prescribing BAK-containing eye drops should be avoided in patients with mitochondrial deficiency, including LHON patients, LHON carriers, and possibly primary open-angle glaucoma patients.
Publication type:JOURNAL ARTICLE
Name of substance:0 (Benzalkonium Compounds); 0 (Ophthalmic Solutions); 0 (Preservatives, Pharmaceutical); 8L70Q75FXE (Adenosine Triphosphate)


  6 / 2049 MEDLINE  
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PMID:28357400
Author:Papakrivou E; Makris D; Manoulakas E; Mitroudi M; Tepetes K; Papazoglou K; Zakynthinos E
Address:Department of Critical Care Medicine, University Hospital of Larissa, University of Thessaly School of Medicine, Larisa, Greece; Department of Pediatric Surgery, General Hospital of "G. Gennimatas", A' University Department, Aristotle University of Thessaloniki, Thessaloniki, Greece.
Title:Intra-Abdominal Hypertension Causes Bacterial Growth in Lungs: An Animal Study.
Source:Biomed Res Int; 2017:4601348, 2017.
ISSN:2314-6141
Country of publication:United States
Language:eng
Abstract:To study the effect of intra-abdominal hypertension (IAH) on the frequency of pneumonia with an experimental study, thirteen Sprague-Dawley rats were included. Eight out of thirteen animals were randomly assigned to receive 10 ml of benzalkonium chloride 0.2% (megacolon group) and five animals received 10 ml NaCl 0.9% (controls). Animals were anaesthetized by intramuscular delivery of ketamine. The incidence of positivity for bacteria lung tissue cultures and mesenteric lymph node cultures was assessed at the 21st day after animals' sacrification, or before in case of death. All megacolon group animals presented progressive increase of the abdomen and increased IAP (≥10 mmHg) whereas the frequency of their evacuations was almost eliminated. Controls presented normal evacuations, no sign of abdominal distention, and normal IAP. In megacolon group animals, there was evidence of significant amount of bacteria in lung cultures. In contrast, no bacteria were found in control animals.
Publication type:JOURNAL ARTICLE
Name of substance:0 (Benzalkonium Compounds)


  7 / 2049 MEDLINE  
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PMID:28355261
Author:Portal C; Gouyer V; Gottrand F; Desseyn JL
Address:LIRIC UMR 995, Univ. Lille, Inserm, CHU Lille, Lille, France.
Title:Preclinical mouse model to monitor live Muc5b-producing conjunctival goblet cell density under pharmacological treatments.
Source:PLoS One; 12(3):e0174764, 2017.
ISSN:1932-6203
Country of publication:United States
Language:eng
Abstract:PURPOSE: Modification of mucous cell density and gel-forming mucin production are established hallmarks of mucosal diseases. Our aim was to develop and validate a mouse model to study live goblet cell density in pathological situations and under pharmacological treatments. METHODS: We created a reporter mouse for the gel-forming mucin gene Muc5b. Muc5b-positive goblet cells were studied in the eye conjunctiva by immunohistochemistry and probe-based confocal laser endomicroscopy (pCLE) in living mice. Dry eye syndrome (DES) model was induced by topical application of benzalkonium chloride (BAK) and recombinant interleukine (rIL) 13 was administered to reverse the goblet cell loss in the DES model. RESULTS: Almost 50% of the total of conjunctival goblet cells are Muc5b+ in unchallenged mice. The decrease density of Muc5b+ conjunctival goblet cell population in the DES model reflects the whole conjunctival goblet cell loss. Ten days of BAK in one eye followed by 4 days without any treatment induced a -18.3% decrease in conjunctival goblet cell density. A four days of rIL13 application in the DES model restored the normal goblet cell density. CONCLUSION: Muc5b is a biological marker of DES mouse models. We bring the proof of concept that our model is unique and allows a better understanding of the mechanisms that regulate gel-forming mucin production/secretion and mucous cell differentiation in the conjunctiva of living mice and can be used to test treatment compounds in mucosal disease models.
Publication type:JOURNAL ARTICLE
Name of substance:0 (Benzalkonium Compounds); 0 (Interleukin-13); 0 (Muc5b protein, mouse); 0 (Mucin-5B); 0 (Recombinant Proteins); 147336-22-9 (Green Fluorescent Proteins)


  8 / 2049 MEDLINE  
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PMID:28257953
Author:Mitani T; Elmarhomy AI; Dulamjav L; Anu E; Saitoh S; Ishida S; Oyama Y
Address:Faculty of Integrated Arts and Sciences, Tokushima University, Tokushima 770-8502, Japan.
Title:Zinc-related actions of sublethal levels of benzalkonium chloride: Potentiation of benzalkonium cytotoxicity by zinc.
Source:Chem Biol Interact; 268:31-36, 2017 Apr 25.
ISSN:1872-7786
Country of publication:Ireland
Language:eng
Abstract:Benzalkonium chloride (BZK) is a common preservative used in pharmaceutical and personal care products. ZnCl was recently reported to significantly potentiate the cytotoxicity of some biocidal compounds. In the present study, therefore, we compared the cytotoxic potency of BZK and then further studied the Zn -related actions of the most cytotoxic agent among BZK, using flow cytometric techniques with appropriate fluorescent probes in rat thymocytes. Cytotoxicity of benzylcetyldimethylammonium (BZK-C16) was more potent that those of benzyldodecyldimethylammonium and benzyldimethyltetradecylammonium. ZnCl (1-10 µM) significantly potentiated the cytotoxicity of BZK-C16 at a sublethal concentration (1 µM). The co-treatment of cells with 3 µM ZnCl and 1 µM BZK-C16 increased the population of both living cells with phosphatidylserine exposed on membrane surfaces and dead cells. BZK-C16 at 0.3-1.0 µM elevated intracellular Zn levels by increasing Zn influx, and augmented the cytotoxicity of 100 µM H O . Zn is concluded to facilitate the toxicity of BZK. We suggest that the toxicity of BZK is determined after taking extracellular (plasma) and/or environmental Zn levels into account.
Publication type:JOURNAL ARTICLE
Name of substance:0 (Benzalkonium Compounds); 0 (Chlorides); 0 (Phosphatidylserines); 0 (Preservatives, Pharmaceutical); 0 (Zinc Compounds); 0 (benzylcetyldimethylammonium); 16287-71-1 (zephiramine); 86Q357L16B (zinc chloride); GAN16C9B8O (Glutathione); N0BN0O8CSL (dimethyldodecylbenzylammonium)


  9 / 2049 MEDLINE  
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PMID:28254642
Author:Huang N; Wang T; Wang WL; Wu QY; Li A; Hu HY
Address:Environmental Simulation and Pollution Control State Key Joint Laboratory, State Environmental Protection Key Laboratory of Microorganism Application and Risk Control (SMARC), School of Environment, Tsinghua University, Beijing, 100084, PR China.
Title:UV/chlorine as an advanced oxidation process for the degradation of benzalkonium chloride: Synergistic effect, transformation products and toxicity evaluation.
Source:Water Res; 114:246-253, 2017 May 01.
ISSN:1879-2448
Country of publication:England
Language:eng
Abstract:Benzalkonium chlorides (BACs), as typical cationic surfactants and biocides widely applied in household and industrial products, have been frequently detected as micropollutants in many aquatic environments. In this study, the combination of UV irradiation and chlorine (UV/chlorine), a newly interested advanced oxidation process, was used to degrade dodecylbenzyldimethylammonium chloride (DDBAC). UV/chlorine showed synergistic effects on DDBAC degradation comparing to UV irradiation or chlorination alone. Radical quenching experiments indicated that degradation of DDBAC by UV/chlorine involved both UV photolysis and radical species oxidation, which accounted for 48.4% and 51.6%, respectively. Chlorine dosage and pH are essential parameters affecting the treatment efficiency of UV/chlorine. The pseudo first order rate constant (k ) increased from 0.046 min to 0.123 min in response to chlorine dosage at 0-150 mg/L, and the degradation percentage of DDBAC within 12 min decreased from 81.4% to 56.6% at pH 3.6-9.5. Five main intermediates were identified and semi-quantified using HPLC-MS/MS and a possible degradation pathway was proposed. The degradation mechanisms of DDBAC by UV/chlorine included cleavage of the benzyl-nitrogen bond and hydrogen abstraction of the alkyl chain. Trichloromethane (TCM), chloral hydrate (CH), trichloropropanone (TCP), dichloropropanone (DCP) and dichloroacetonitrile (DCAN) were detected using GC-ECD. The formation of chlorinated products increased rapidly initially, then decreased (TCM, TCP, DCP and DCAN) or remained stable (CH) with extended treatment. The actual formation of TCM peaked at 30 min (50.3 µg/L), while other chlorinated products did not exceed 10 µg/L throughout the process. Based on the luminescent bacterial assay, DDBAC solution underwent almost complete detoxification subjected to UV/chlorine treatment for 120 min, which is more effective than UV irradiation or chlorination alone.
Publication type:JOURNAL ARTICLE
Name of substance:0 (Benzalkonium Compounds); 0 (Water Pollutants, Chemical); 4R7X1O2820 (Chlorine)


  10 / 2049 MEDLINE  
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PMID:28245636
Author:Yang Q; Zhang Y; Liu X; Wang N; Song Z; Wu K
Address:Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou 510060, China. muyangmay@126.com.
Title:A Comparison of the Effects of Benzalkonium Chloride on Ocular Surfaces between C57BL/6 and BALB/c Mice.
Source:Int J Mol Sci; 18(3), 2017 Feb 26.
ISSN:1422-0067
Country of publication:Switzerland
Language:eng
Abstract:Models of benzalkonium chloride (BAC)-induced ocular disruption have been created and are widely used in various animals. This study aimed to compare the effects of BAC on the ocular surfaces of C57BL/6 and BALB/c mice. C57BL/6 and BALB/c mice were treated separately with BAC eye-drops at different concentrations. Eyes were evaluated by scoring epithelial disruption, corneal opacity and neovascularization in vivo, and by histological assays with hematoxylin/eosin (H/E) and periodic acid-Schiff stainings and by determining the expression of inflammatory factors in vitro on Days 7 and 14. The in vivo corneal epithelial disruption, corneal edema/opacity and neovascularization, which were in accordance with the results of the H/E staining and peaked at Day 7, were observed in a dose-dependent manner in the BAC-treated mice, with more severe signs in the C57BL/6 mice than the BALB/c mice. The loss of conjunctival goblet cells in the conjunctivas and the increasing expression of monocyte chemoattractant protein 1 (MCP-1), growth-regulated protein alpha (GROa) and macrophage inflammatory protein-1 alpha (MIP-1a) in the corneas were found in a dose-dependent manner in both strains of mice. Topical application of BAC can dramatically disrupt the ocular surfaces of C57BL/6 and BALB/c mice, and the disruptions were much more severe in the C57BL/6 mice that received high doses of BAC.
Publication type:JOURNAL ARTICLE
Name of substance:0 (Anti-Infective Agents, Local); 0 (Benzalkonium Compounds); 0 (Inflammation Mediators); 0 (Ophthalmic Solutions)



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