Benzalkonium chloride(BAC)is widely employed as a broad-spectrum biocide and has emerged as a significant environmental pollutant.Polymyxin B(PB)serves as the last-line defense for the treatment of Gram-negative patho...Benzalkonium chloride(BAC)is widely employed as a broad-spectrum biocide and has emerged as a significant environmental pollutant.Polymyxin B(PB)serves as the last-line defense for the treatment of Gram-negative pathogens.Previous studies reported that BAC-adapted Pseudomonas aeruginosa increased the tolerance to PB.Herein,we present the novel finding that the combination of BAC and PB exhibited synergistic antibacterial effects against P.aeruginosa.Time-killing assay demonstrated a significant reduction in bacterial cell viability.Scanning electron microscopy,zeta potential analysis,hydrophobicity measurements,and fluorescence probe analyses collectively revealed severe disruption of the cell envelope and membrane potential induced by the combination of BAC and PB.Transcriptomic analysis revealed that the BAC-PB combination notably downreg-ulated the expression of genes involved in lipid A modification and cell envelope production,including phoPQ,pmrAB,bamABCDE,lptABCDEG,lolB,yidC,and murJ.Additionally,the combination group exhibited augmented production of reactive oxygen species and diminished ATP synthesis.The expression of the genes associated with substance metabolism and energy generation was significantly impeded.This study provides significant implica-tions for the interactions of biocides and antibiotics on Gram-negative pathogens,while also addressing antibiotic resistance and developing the external treatment strategy for Pseudomonas-infected wounds and burns.展开更多
Background: This study investigated the safety (cytotoxicity in vitro) and pharmacological effects (ocular hypotensive effects and aqueous humor concentrations in normotensive monkeys in vivo) of latanoprost formulati...Background: This study investigated the safety (cytotoxicity in vitro) and pharmacological effects (ocular hypotensive effects and aqueous humor concentrations in normotensive monkeys in vivo) of latanoprost formulations with benzalkonium chloride (latanoprost with BAK) and without BAK (NP). Methods: A bioequivalence study of latanoprost with BAK and NP was also conducted on human healthy volunteers. Cytotoxicity and the protective effect against H2O2 stress in vitro were evaluated using human corneal epithelial cells. The ocular hypotensive effects in normotensive monkeys were measured by pneumatonometer and the aqueous humor concentrations of latanoprost free acid were determined by liquid chromatography/mass spectrum (LC/MS) methods. The bioequivalence study of latanoprost with BAK and NP was carried out as a single eye drop, two-sequence, crossover randomized study. Results: Cytotoxicity tests in vitro revealed that NP was less toxic than latanoprost with BAK and significantly inhibited H2O2 induced cell damage while latanoprost with BAK did not. The hypotensive efficacy and the latanoprost free acid concentrations in aqueous humor of each formulation were not significantly different in monkeys. In the bioequivalence study, NP was bioequivalent to latanoprost with BAK. NP was safer than latanoprost with BAK with respect the results obtained in the in vitro cytotoxicity test. There was no difference observed between latanoprost with BAK and NP in the IOP lowering effect in monkeys and healthy volunteers. Conclusion: Taken together, these results indicate that NP is as effective as latanoprost with BAK, and is more likely to maintain ocular surface health than latanoprost with BAK.展开更多
In this work,a surfactant,benzalkonium chloride(BAC),was used to study its effects on both the growth of Chlorella vulgaris and the corrosion caused by its biofilm.Experimental results indicated that BAC at a low conc...In this work,a surfactant,benzalkonium chloride(BAC),was used to study its effects on both the growth of Chlorella vulgaris and the corrosion caused by its biofilm.Experimental results indicated that BAC at a low concentration of 3 mg/L suppressed C.vulgaris growth and achieved 81%corrosion inhibition based on weight loss reduction.The inhibition effects increased when the BAC dosage was increased.At 30 mg/L,the corrosion inhibition increased to 95%.Electrochemical results supported surface pitting analysis,weight loss results data and confirmed the corrosion inhibition.展开更多
A high-performance liquid chromatography （HPLC） system was used in the reversed phase mode for the determination ofbenzalkonium chloride （BKC） in azithromycin viscous ophthalmic drops. A Venusil-XBP（L）-C18 （150...A high-performance liquid chromatography （HPLC） system was used in the reversed phase mode for the determination ofbenzalkonium chloride （BKC） in azithromycin viscous ophthalmic drops. A Venusil-XBP（L）-C18 （150 mm×4.6 mm, 5 gm） column was used at 50℃. The mobile phase consisted of a mixture of methanol-potassium phosphate （16：5, v/v）. Two sample preparation methods were compared. The results suggested that, compared with an extraction procedure, a deproteinization procedure was much quicker and more convenient. Using the deproteinization procedure for sample preparation, calibration curves were linear in the range 5.0-50μg/ml. The within-day and inter-day coefficients of variation were less than 10%. The average recoveries were determined as 96.70%, 98.52%, and 97.96% at concentrations of 10.0, 30.0, and 50.0 μg/ml, respectively. Variability in precision did not exceed 5%. In conclusion, this HPLC method using a simple sample treatment procedure appears suitable for monitoring BKC content in azithromycin viscous ophthalmic drops.展开更多
Objective To develop an optimized BZK gel with good pharmaceutical effect and less toxicity to vaginal mucosa. Methods Four methods as below were used to research the spermicidal activity of BZK gel： 1） in vitro spe...Objective To develop an optimized BZK gel with good pharmaceutical effect and less toxicity to vaginal mucosa. Methods Four methods as below were used to research the spermicidal activity of BZK gel： 1） in vitro spermicidal test; 2） in vivo spermicidal test in rabbits; 3） anti-fertility test in rabbits; 4） contraceptive test in rabbits. Mucosal irritation test was used in rats to evaluate the safety of optimized BZK gel. Microbiological assessments were used to research anti-STI pathogens （including treponema pallidum, neisseria gonorrhoeae, trichomona vaginalis, candida albicans, ureaplama urealyticum, herpes simplex virus type-2, chlamydiae trachomatis） effect of optimized BZK gel. Results In vitro spermicidal test, EC50 of BZK gel was 0.029mg/ml, a little higher than that of N-9 （0.019mg/ml）. The MIC of BZK gel was 0.25mg/ml, similar to that of N-9 （0.20mg/ml）. The vaginal mucosal irritation test in rats showed that 0.429% BZK gel showed only minimal vaginal irritation, and did not damage the vaginal epithelium or cause local inflammation in rats. Microbiological assessments showed that optimized BZK gel could inhibit or inactivate common ST1 pathogens even after 3-fold or 5-fold dilution. Conclusion Optimized BZK gel was an effective microbicides.展开更多
A modified selective medium (modified Cetrimide Agar, mCA) consisting of 200 μg/mL benzalkonium chloride (BKC) was developed for the isolation of Pseudomonas aeruginosa from raw milk. Initially, a total of 55 isolate...A modified selective medium (modified Cetrimide Agar, mCA) consisting of 200 μg/mL benzalkonium chloride (BKC) was developed for the isolation of Pseudomonas aeruginosa from raw milk. Initially, a total of 55 isolates were obtained from 14 raw milk samples collected from several dairy plants in Ankara, Turkey. Among these isolates, 19 were identified as Pseudomonas aeruginosa, 28 as Pseudomonas fluorescens, 4 as Acinetobacter baumannii, 2 as Enterobacter intermedium, 1 asEnterobacter agglomerans, and 1 as Escherichia coli using Microbact biochemical test kit. BKC was chosen as a selective agent to suppress growth of competitive flora because it is very effective against a wide range of Gram-negative bacteria while P. aeruginosa is resistant. MICs (minimum inhibitory concentration) for BKC were determined by agar dilution method. The concentration of 200 μg/mL BKC inhibited competitive flora, while 90% of P. aeruginosa strains were resistant. When the results of enumeration of P. aeruginosa and other Gram (-) bacteria in Cetrimide Agar (CA) and mCA were compared, it was observed that mCA was more selective than the standard CA in preventing the growth of competitive flora especially of P. fluorescens.展开更多
Aims: The representativeness of the mandatory bacterial strains specified in European standards for in vitro assay of the bactericidal activity of antiseptics was evaluated by testing the activity of an antiseptic com...Aims: The representativeness of the mandatory bacterial strains specified in European standards for in vitro assay of the bactericidal activity of antiseptics was evaluated by testing the activity of an antiseptic combining chlorhexidine digluconate 0.2% and benzalkonium chloride 0.5% against 21 additional bacterial strains, and the positive interaction between these two biocidal agents was assessed. Methods and Results: The bactericidal activity of the antiseptic solution used pure or diluted was assessed according to the European standards EN 1040 and EN 13727. The contact time was 1 min at 20°C. Interfering substances used in the EN 13727 assay were bovine serum albumin and sheep erythrocytes, simulating “dirty” conditions, and hard water. A reduction of colony-forming units by ≥5 log10 was deemed to meet the requirements to conclude bactericidal activity. Under “basic” conditions, the bactericidal activity of the antiseptic was observed against all four mandatory strains specified in the standards as well as against nearly all the additional strains tested, including most of those with acquired antibiotic-resistance. The positive interaction between the two biocidal agents was also confirmed. Under “dirty” conditions, the bactericidal activity of the antiseptic solution was maintained against all the mandatory strains and was reduced against only four of the additional strains tested. Conclusions: With regard to the antiseptic tested and under the experimental conditions described, bactericidal activity evidenced against the mandatory strains appeared to be representative of that manifested against a wide range of the main pathogenic bacteria. Reduced bacterial activity against some of the additional strains tested (e.g. Enterobacteriaceae) was observed under “dirty” conditions. Significance and Impact of the Study: EN 13727 with some experimental adjustments represents an additional appropriate standard that needs to be considered for mucocutaneous antiseptic assessment. However, it may be worth including other specific bacterial strains to those specified in the standard, when evaluating antiseptics intended for use in certain clinical situations.展开更多
Objective:To explore the safety and efficacy of eye drops without benzalkonium chloride(BAK)in treating glaucoma and ocular hypertension.Methods:The clinical case-control literatures about eye drops without BAK treati...Objective:To explore the safety and efficacy of eye drops without benzalkonium chloride(BAK)in treating glaucoma and ocular hypertension.Methods:The clinical case-control literatures about eye drops without BAK treating glaucoma and ocular hypertension were retrieved in PubMed,EMBASE,Cochrane and Chinese Biological and Medical database.Mela 5.0 software was used to analyze the literatures.Results:Five clinical control studies were included.The results indicated both eye drops could lower the intraocular pressure,and the intraocular pressurelowering difference between two eye drops was 0.07 mmHg(95%CI:0.04,0.19)(P>0.05).Two adverse reactions occurred more were conjunctival injection(10.78%)and allergic conjunctivitis(4.78%).The odd ratio of two eye drops occurring conjunctival injection and allergic conjunctivitis was 0.67(95%CI,0.25,1.10)and 0.82(95%CI,0.09,1.54),respectively(P<0.05)in fixed effect model.Conclusions:There is no difference between the eye drops with or without BAK in lowering intraocular pressure.but the latter is of higher safety.In consideration of the relatively small sample size of this research,more high-quality clinical research contrasts are needed as evidence.展开更多
As one typical cationic disinfectant, quaternary ammonium compounds(QACs) were approved for surface disinfection in the coronavirus disease 2019 pandemic and then unintentionally or intentionally released into the sur...As one typical cationic disinfectant, quaternary ammonium compounds(QACs) were approved for surface disinfection in the coronavirus disease 2019 pandemic and then unintentionally or intentionally released into the surrounding environment. Concerningly, it is still unclear how the soil microbial community succession happens and the nitrogen(N)cycling processes alter when exposed to QACs. In this study, one common QAC(benzalkonium chloride(BAC) was selected as the target contaminant, and its effects on the temporal changes in soil microbial community structure and nitrogen transformation processes were determined by q PCR and 16S r RNA sequencing-based methods. The results showed that the aerobic microbial degradation of BAC in the two different soils followed first-order kinetics with a half-life(4.92 vs. 17.33 days) highly dependent on the properties of the soil. BAC activated the abundance of N fixation gene(nif H) and nitrification genes(AOA and AOB) in the soil and inhibited that of denitrification gene(nar G). BAC exposure resulted in the decrease of the alpha diversity of soil microbial community and the enrichment of Crenarchaeota and Proteobacteria. This study demonstrates that BAC degradation is accompanied by changes in soil microbial community structure and N transformation capacity.展开更多
Members of the Pseudomonas family are commonly found in nature, some species are pathogenic for humans, as well as being resistant to multiple disinfectants. Various studies have revealed that benzalkonium chloride (B...Members of the Pseudomonas family are commonly found in nature, some species are pathogenic for humans, as well as being resistant to multiple disinfectants. Various studies have revealed that benzalkonium chloride (BKC) has an inhibitory effect on many bacteria but it has no significant effect on Pseudomonas aeruginosa. Cetrimide agar medium is recommended for the isolation and enumeration of Ps. aeruginosa in food and environmental samples. However, there are claims that for some food factories and in particular the bottled water industry, the selectivity of this medium is not sufficient. The aim of the current research is the creation of a more selective medium for Ps. aeruginosa with BKC. A total of 28 isolates were isolated with Cetrimide agar from raw water samples and identified using biochemical tests and commercial identification kits. All the bacteria were inoculated in Cetrimide agar plates containing 0 - 625 μg/mL BKC. The Petri dishes were incubated at 37°C and 42°C for 24 h. The results showed that 375 μg/mL BKC was sufficient to suppress Burk. pseudomallei at both incubation temperatures. Ps. fluorescens-35 could not grow at 42°C at any concentration, including the control, and was suppressed at 500 μg/mL BKC. All the Ps. aeruginosa isolates and control strain were grown at both incubation temperatures at 375 μg/mL BKC concentration. In conclusion, the analysis of Ps. aeruginosa showed that the growth of accompanying flora may be suppressed by adding 375-μg/mL BKC into Cetrimide agar and incubating at an elevated temperature of 42°C.展开更多
Background:The goal was to explore the protective effect and potential mechanism of amniotic membrane extracts(AME)on the ocular surface exposed to benzalkonium chloride(BAC).Methods:The human corneal epithelial cell(...Background:The goal was to explore the protective effect and potential mechanism of amniotic membrane extracts(AME)on the ocular surface exposed to benzalkonium chloride(BAC).Methods:The human corneal epithelial cell(HCEC)line SD-HCEC1s was cultured in 5 groups:normal control(NC),NC+AME,BAC,BAC+NC,and BAC+AME.Cell viability analysis,flow cytometry analysis,real-time polymerase chain reaction(PCR),and western blot were employed to measure changes in cell function.Matrix metalloproteinases(MMPs)and inflammatory cytokines were assayed by enzyme-linked immunosorbent assay(ELISA)and activity assays.Results:Real-time PCR and western blot analysis demonstrated that the expressional level of caspase-8 was increased while the levels of Muc1,Muc4,and Muc16 were decreased after treatment with 0.02%BAC for 1 h.When the SD-HCEC1s were withdrawn from the BAC and switched to media containing 10%AME for 2 days,the expression level of capsase-8 was decreased while the levels of Muc1,Muc4,and Muc16 were increased.Real-time PCR and ELISA demonstrated that the mRNA and protein levels of MMP-1,MMP-3,MMP-13,CXCL1,interleukin(IL)-1β,IL-6,and tumor necrosis factor-alpha(TNF-α)were significantly increased after treatment with 0.02%BAC,whereas those of MMP-8 were decreased.When the 0.02%BAC was withdrawn and the SD-HCEC1s were cultured in 10%AME,the mRNA and protein levels of MMP-1,MMP-3,MMP-13,CXCL1,IL-1β,IL-6,and TNF-αwere decreased,while those of MMP-8 were increased.MMP-8 activity assays confirmed that IL-1βand TNF-αdownregulated the protein levels of MMP-8.Conclusions:AME protects SD-HCEC1s when stressed in BAC via upregulation of MMP-8 and downregulation of IL-1βand TNF-α.AME may have the potential functions to be employed as a topical adjunctive therapy in eyes chronically exposed to BAC.展开更多
Background： Long-term use of benzalkonium chloride （BAC）-preserved drugs is often associated with ocular surface toxicity. Ocular surface symptoms had a substantial impact on the glaucoma patients＇ quality of life...Background： Long-term use of benzalkonium chloride （BAC）-preserved drugs is often associated with ocular surface toxicity. Ocular surface symptoms had a substantial impact on the glaucoma patients＇ quality of life and compliance. This study aimed to investigate the effects of sodium hyaluronate （SH） on ocular surface toxicity induced by BAC-preserved anti-glaucoma medications treatment. Methods： Filly-eight patients （101 eyes）, who received topical BAC-preserved anti-glaucoma medications treatment and met the severe dry eye criteria, were included in the analysis. All patients were maintained the original topical anti-glaucoma treatment. In the SH-treated group （56 eyes）, unpreserved 0.3% SH eye drops were administered with 3 times daily for 90 days. In the control group （55 eyes）, phosphate-butTered saline were administered with 3 times daily for 90 days. Ocular Surface Disease Index （OSDI） questionnaire, break-up time （BUT） test, corneal fluorescein staining, corneal and conjunctival rose Bengal staining, Schirmer test, and conjunctiva impression cytology were pertbrmed sequentially on days 0 and 91. Results： Compared with the control group, SH-treated group showed decrease in OSDI scores （Kruskal-Wallis test： H = 38.668, P 〈 0.001 ）, fluorescein and rose Bengal scores （Wilcoxon signed-ranks test： z = -3.843, P 〈 0.001, and z = 3.508, P 〈 0.001, respectively）, increase in tear fihn BUT （t-test： t - -10.994, P 〈 0.001 ） and aqueous tear production （t-test： t = -10.328, P 〈 0.001 ） on day 91. The goblet cell density was increased （t-test： t = -9.981, P 〈 0.001）, and the morphology of the conjunctival epithelium were also improved after SH treatment. Conclusions： SH significantly improved both symptoms and signs of ocular surface damage in patients with BAC-preserved anti-glaucoma medications treatment. SH could be proposed as a new attempt to reduce ocular surface toxicity, and alleviate symptoms of ocular surface damage in BAC-preserved anti-glaucoma medications treatment.展开更多
Objective:To investigate the anti-inflammatory,antioxidant,and goblet cell-stimulating effects of a suspension of Ophiopogon japonicus(L.f.)Ker Gawl.(O.japonicus,Mai Dong)extract combined with hyaluronic acid(HA)in th...Objective:To investigate the anti-inflammatory,antioxidant,and goblet cell-stimulating effects of a suspension of Ophiopogon japonicus(L.f.)Ker Gawl.(O.japonicus,Mai Dong)extract combined with hyaluronic acid(HA)in the mouse model with dry eye disease(DED).Methods:A DED mouse model was induced using benzalkonium chloride(BAK),followed by treatment with O.japonicus extract-containing eye drops at varying concentrations.Experimental groups included a normal control,a DED model control,a positive control,and an O.japonicus extract-treated group.Corneal fluorescein staining and tear break-up time(TBUT)were used to assess tear film stability and ocular surface integrity.Enzyme-linked immunosorbent assay(ELISA)measured inflammatory factor levels in corneal and conjunctival tissues,whereas Western blot(WB)analyzed key antioxidant and inflammatory markers,including nuclear factor erythroid 2-related factor(2Nrf2)and heme oxygenase 1(HO-1).Periodic acid-schiff(PAS)staining and immunofluorescence were used to evaluate goblet cell density and mucin secretion.Results:O.japonicus extract significantly improved corneal damage,reduced fluorescein staining scores,prolonged TBUT,and increased tear secretion.It downregulated inflammatory markers,including interleukin-8(IL-8),interleukin-1β(IL-1β),and interferon-g(IFN-γ)while upregulating Nrf2,HO-1,and the interleukin-13(IL-13)/IFN-γ ratio,alleviating oxidative stress and inflammation.PAS staining showed increased conjunctival goblet cell density and restored mucin secretion,enhancing tear film stability.Conclusion:O.japonicus extract demonstrated significant anti-inflammatory,antioxidant,and goblet cell-stimulating effects in a DED model,with good biocompatibility and promising therapeutic potential.Future research should optimize extraction processes and validate their efficacy and safety in clinical settings.展开更多
基金supported by the National Natural Science Foundation of China(No.32170121).
文摘Benzalkonium chloride(BAC)is widely employed as a broad-spectrum biocide and has emerged as a significant environmental pollutant.Polymyxin B(PB)serves as the last-line defense for the treatment of Gram-negative pathogens.Previous studies reported that BAC-adapted Pseudomonas aeruginosa increased the tolerance to PB.Herein,we present the novel finding that the combination of BAC and PB exhibited synergistic antibacterial effects against P.aeruginosa.Time-killing assay demonstrated a significant reduction in bacterial cell viability.Scanning electron microscopy,zeta potential analysis,hydrophobicity measurements,and fluorescence probe analyses collectively revealed severe disruption of the cell envelope and membrane potential induced by the combination of BAC and PB.Transcriptomic analysis revealed that the BAC-PB combination notably downreg-ulated the expression of genes involved in lipid A modification and cell envelope production,including phoPQ,pmrAB,bamABCDE,lptABCDEG,lolB,yidC,and murJ.Additionally,the combination group exhibited augmented production of reactive oxygen species and diminished ATP synthesis.The expression of the genes associated with substance metabolism and energy generation was significantly impeded.This study provides significant implica-tions for the interactions of biocides and antibiotics on Gram-negative pathogens,while also addressing antibiotic resistance and developing the external treatment strategy for Pseudomonas-infected wounds and burns.
文摘Background: This study investigated the safety (cytotoxicity in vitro) and pharmacological effects (ocular hypotensive effects and aqueous humor concentrations in normotensive monkeys in vivo) of latanoprost formulations with benzalkonium chloride (latanoprost with BAK) and without BAK (NP). Methods: A bioequivalence study of latanoprost with BAK and NP was also conducted on human healthy volunteers. Cytotoxicity and the protective effect against H2O2 stress in vitro were evaluated using human corneal epithelial cells. The ocular hypotensive effects in normotensive monkeys were measured by pneumatonometer and the aqueous humor concentrations of latanoprost free acid were determined by liquid chromatography/mass spectrum (LC/MS) methods. The bioequivalence study of latanoprost with BAK and NP was carried out as a single eye drop, two-sequence, crossover randomized study. Results: Cytotoxicity tests in vitro revealed that NP was less toxic than latanoprost with BAK and significantly inhibited H2O2 induced cell damage while latanoprost with BAK did not. The hypotensive efficacy and the latanoprost free acid concentrations in aqueous humor of each formulation were not significantly different in monkeys. In the bioequivalence study, NP was bioequivalent to latanoprost with BAK. NP was safer than latanoprost with BAK with respect the results obtained in the in vitro cytotoxicity test. There was no difference observed between latanoprost with BAK and NP in the IOP lowering effect in monkeys and healthy volunteers. Conclusion: Taken together, these results indicate that NP is as effective as latanoprost with BAK, and is more likely to maintain ocular surface health than latanoprost with BAK.
基金supported by National Key Research and Development Program of China(2018YFF0215002)Graduates’Innovation Fund of Huazhong University of Science and Technology(5003013044)+2 种基金The Open Fund of Hubei Key Laboratory of Materials Chemistry and Service Failure(2017)Key Laboratory of Materials Chemistry for Energy Conversion and Storage,Ministry of Education(2018)Natural Science Foundation of the Jiangsu Higher Education Institutions of China(No.18KJB530004)。
文摘In this work,a surfactant,benzalkonium chloride(BAC),was used to study its effects on both the growth of Chlorella vulgaris and the corrosion caused by its biofilm.Experimental results indicated that BAC at a low concentration of 3 mg/L suppressed C.vulgaris growth and achieved 81%corrosion inhibition based on weight loss reduction.The inhibition effects increased when the BAC dosage was increased.At 30 mg/L,the corrosion inhibition increased to 95%.Electrochemical results supported surface pitting analysis,weight loss results data and confirmed the corrosion inhibition.
基金Project (No. 2008BAI55B03) supported by the Key Project of the National Science and Technology Pillar Program, China
文摘A high-performance liquid chromatography （HPLC） system was used in the reversed phase mode for the determination ofbenzalkonium chloride （BKC） in azithromycin viscous ophthalmic drops. A Venusil-XBP（L）-C18 （150 mm×4.6 mm, 5 gm） column was used at 50℃. The mobile phase consisted of a mixture of methanol-potassium phosphate （16：5, v/v）. Two sample preparation methods were compared. The results suggested that, compared with an extraction procedure, a deproteinization procedure was much quicker and more convenient. Using the deproteinization procedure for sample preparation, calibration curves were linear in the range 5.0-50μg/ml. The within-day and inter-day coefficients of variation were less than 10%. The average recoveries were determined as 96.70%, 98.52%, and 97.96% at concentrations of 10.0, 30.0, and 50.0 μg/ml, respectively. Variability in precision did not exceed 5%. In conclusion, this HPLC method using a simple sample treatment procedure appears suitable for monitoring BKC content in azithromycin viscous ophthalmic drops.
文摘Objective To develop an optimized BZK gel with good pharmaceutical effect and less toxicity to vaginal mucosa. Methods Four methods as below were used to research the spermicidal activity of BZK gel： 1） in vitro spermicidal test; 2） in vivo spermicidal test in rabbits; 3） anti-fertility test in rabbits; 4） contraceptive test in rabbits. Mucosal irritation test was used in rats to evaluate the safety of optimized BZK gel. Microbiological assessments were used to research anti-STI pathogens （including treponema pallidum, neisseria gonorrhoeae, trichomona vaginalis, candida albicans, ureaplama urealyticum, herpes simplex virus type-2, chlamydiae trachomatis） effect of optimized BZK gel. Results In vitro spermicidal test, EC50 of BZK gel was 0.029mg/ml, a little higher than that of N-9 （0.019mg/ml）. The MIC of BZK gel was 0.25mg/ml, similar to that of N-9 （0.20mg/ml）. The vaginal mucosal irritation test in rats showed that 0.429% BZK gel showed only minimal vaginal irritation, and did not damage the vaginal epithelium or cause local inflammation in rats. Microbiological assessments showed that optimized BZK gel could inhibit or inactivate common ST1 pathogens even after 3-fold or 5-fold dilution. Conclusion Optimized BZK gel was an effective microbicides.
文摘A modified selective medium (modified Cetrimide Agar, mCA) consisting of 200 μg/mL benzalkonium chloride (BKC) was developed for the isolation of Pseudomonas aeruginosa from raw milk. Initially, a total of 55 isolates were obtained from 14 raw milk samples collected from several dairy plants in Ankara, Turkey. Among these isolates, 19 were identified as Pseudomonas aeruginosa, 28 as Pseudomonas fluorescens, 4 as Acinetobacter baumannii, 2 as Enterobacter intermedium, 1 asEnterobacter agglomerans, and 1 as Escherichia coli using Microbact biochemical test kit. BKC was chosen as a selective agent to suppress growth of competitive flora because it is very effective against a wide range of Gram-negative bacteria while P. aeruginosa is resistant. MICs (minimum inhibitory concentration) for BKC were determined by agar dilution method. The concentration of 200 μg/mL BKC inhibited competitive flora, while 90% of P. aeruginosa strains were resistant. When the results of enumeration of P. aeruginosa and other Gram (-) bacteria in Cetrimide Agar (CA) and mCA were compared, it was observed that mCA was more selective than the standard CA in preventing the growth of competitive flora especially of P. fluorescens.
文摘Aims: The representativeness of the mandatory bacterial strains specified in European standards for in vitro assay of the bactericidal activity of antiseptics was evaluated by testing the activity of an antiseptic combining chlorhexidine digluconate 0.2% and benzalkonium chloride 0.5% against 21 additional bacterial strains, and the positive interaction between these two biocidal agents was assessed. Methods and Results: The bactericidal activity of the antiseptic solution used pure or diluted was assessed according to the European standards EN 1040 and EN 13727. The contact time was 1 min at 20°C. Interfering substances used in the EN 13727 assay were bovine serum albumin and sheep erythrocytes, simulating “dirty” conditions, and hard water. A reduction of colony-forming units by ≥5 log10 was deemed to meet the requirements to conclude bactericidal activity. Under “basic” conditions, the bactericidal activity of the antiseptic was observed against all four mandatory strains specified in the standards as well as against nearly all the additional strains tested, including most of those with acquired antibiotic-resistance. The positive interaction between the two biocidal agents was also confirmed. Under “dirty” conditions, the bactericidal activity of the antiseptic solution was maintained against all the mandatory strains and was reduced against only four of the additional strains tested. Conclusions: With regard to the antiseptic tested and under the experimental conditions described, bactericidal activity evidenced against the mandatory strains appeared to be representative of that manifested against a wide range of the main pathogenic bacteria. Reduced bacterial activity against some of the additional strains tested (e.g. Enterobacteriaceae) was observed under “dirty” conditions. Significance and Impact of the Study: EN 13727 with some experimental adjustments represents an additional appropriate standard that needs to be considered for mucocutaneous antiseptic assessment. However, it may be worth including other specific bacterial strains to those specified in the standard, when evaluating antiseptics intended for use in certain clinical situations.
基金supported by Science and Technology Research Projects of Henan Province(991170529)
文摘Objective:To explore the safety and efficacy of eye drops without benzalkonium chloride(BAK)in treating glaucoma and ocular hypertension.Methods:The clinical case-control literatures about eye drops without BAK treating glaucoma and ocular hypertension were retrieved in PubMed,EMBASE,Cochrane and Chinese Biological and Medical database.Mela 5.0 software was used to analyze the literatures.Results:Five clinical control studies were included.The results indicated both eye drops could lower the intraocular pressure,and the intraocular pressurelowering difference between two eye drops was 0.07 mmHg(95%CI:0.04,0.19)(P>0.05).Two adverse reactions occurred more were conjunctival injection(10.78%)and allergic conjunctivitis(4.78%).The odd ratio of two eye drops occurring conjunctival injection and allergic conjunctivitis was 0.67(95%CI,0.25,1.10)and 0.82(95%CI,0.09,1.54),respectively(P<0.05)in fixed effect model.Conclusions:There is no difference between the eye drops with or without BAK in lowering intraocular pressure.but the latter is of higher safety.In consideration of the relatively small sample size of this research,more high-quality clinical research contrasts are needed as evidence.
基金supported by the National Natural Science Foundation of China (No. 42177363)the National Key R&D Program of China (No. 2019YFC1805502)+1 种基金the Open Project of National and Local Joint Engineering Research Center of Shale Gas Exploration and Development (No. YYQKTKFGJDFLHGCYJZX-201904)the Innovation Support Program for Chongqing Overseas Returnees (2017)。
文摘As one typical cationic disinfectant, quaternary ammonium compounds(QACs) were approved for surface disinfection in the coronavirus disease 2019 pandemic and then unintentionally or intentionally released into the surrounding environment. Concerningly, it is still unclear how the soil microbial community succession happens and the nitrogen(N)cycling processes alter when exposed to QACs. In this study, one common QAC(benzalkonium chloride(BAC) was selected as the target contaminant, and its effects on the temporal changes in soil microbial community structure and nitrogen transformation processes were determined by q PCR and 16S r RNA sequencing-based methods. The results showed that the aerobic microbial degradation of BAC in the two different soils followed first-order kinetics with a half-life(4.92 vs. 17.33 days) highly dependent on the properties of the soil. BAC activated the abundance of N fixation gene(nif H) and nitrification genes(AOA and AOB) in the soil and inhibited that of denitrification gene(nar G). BAC exposure resulted in the decrease of the alpha diversity of soil microbial community and the enrichment of Crenarchaeota and Proteobacteria. This study demonstrates that BAC degradation is accompanied by changes in soil microbial community structure and N transformation capacity.
文摘Members of the Pseudomonas family are commonly found in nature, some species are pathogenic for humans, as well as being resistant to multiple disinfectants. Various studies have revealed that benzalkonium chloride (BKC) has an inhibitory effect on many bacteria but it has no significant effect on Pseudomonas aeruginosa. Cetrimide agar medium is recommended for the isolation and enumeration of Ps. aeruginosa in food and environmental samples. However, there are claims that for some food factories and in particular the bottled water industry, the selectivity of this medium is not sufficient. The aim of the current research is the creation of a more selective medium for Ps. aeruginosa with BKC. A total of 28 isolates were isolated with Cetrimide agar from raw water samples and identified using biochemical tests and commercial identification kits. All the bacteria were inoculated in Cetrimide agar plates containing 0 - 625 μg/mL BKC. The Petri dishes were incubated at 37°C and 42°C for 24 h. The results showed that 375 μg/mL BKC was sufficient to suppress Burk. pseudomallei at both incubation temperatures. Ps. fluorescens-35 could not grow at 42°C at any concentration, including the control, and was suppressed at 500 μg/mL BKC. All the Ps. aeruginosa isolates and control strain were grown at both incubation temperatures at 375 μg/mL BKC concentration. In conclusion, the analysis of Ps. aeruginosa showed that the growth of accompanying flora may be suppressed by adding 375-μg/mL BKC into Cetrimide agar and incubating at an elevated temperature of 42°C.
基金This study was supported by the“Yangcheng Scholar”Youth Research Backbone Training Project of Guangzhou Municipal College(No.1201581612)Guangzhou Science and Technology Project(No.201804010038)Guangdong Natural Science Foundation of China(2020A1515010276,No.2015A030313479).
文摘Background:The goal was to explore the protective effect and potential mechanism of amniotic membrane extracts(AME)on the ocular surface exposed to benzalkonium chloride(BAC).Methods:The human corneal epithelial cell(HCEC)line SD-HCEC1s was cultured in 5 groups:normal control(NC),NC+AME,BAC,BAC+NC,and BAC+AME.Cell viability analysis,flow cytometry analysis,real-time polymerase chain reaction(PCR),and western blot were employed to measure changes in cell function.Matrix metalloproteinases(MMPs)and inflammatory cytokines were assayed by enzyme-linked immunosorbent assay(ELISA)and activity assays.Results:Real-time PCR and western blot analysis demonstrated that the expressional level of caspase-8 was increased while the levels of Muc1,Muc4,and Muc16 were decreased after treatment with 0.02%BAC for 1 h.When the SD-HCEC1s were withdrawn from the BAC and switched to media containing 10%AME for 2 days,the expression level of capsase-8 was decreased while the levels of Muc1,Muc4,and Muc16 were increased.Real-time PCR and ELISA demonstrated that the mRNA and protein levels of MMP-1,MMP-3,MMP-13,CXCL1,interleukin(IL)-1β,IL-6,and tumor necrosis factor-alpha(TNF-α)were significantly increased after treatment with 0.02%BAC,whereas those of MMP-8 were decreased.When the 0.02%BAC was withdrawn and the SD-HCEC1s were cultured in 10%AME,the mRNA and protein levels of MMP-1,MMP-3,MMP-13,CXCL1,IL-1β,IL-6,and TNF-αwere decreased,while those of MMP-8 were increased.MMP-8 activity assays confirmed that IL-1βand TNF-αdownregulated the protein levels of MMP-8.Conclusions:AME protects SD-HCEC1s when stressed in BAC via upregulation of MMP-8 and downregulation of IL-1βand TNF-α.AME may have the potential functions to be employed as a topical adjunctive therapy in eyes chronically exposed to BAC.
文摘Background： Long-term use of benzalkonium chloride （BAC）-preserved drugs is often associated with ocular surface toxicity. Ocular surface symptoms had a substantial impact on the glaucoma patients＇ quality of life and compliance. This study aimed to investigate the effects of sodium hyaluronate （SH） on ocular surface toxicity induced by BAC-preserved anti-glaucoma medications treatment. Methods： Filly-eight patients （101 eyes）, who received topical BAC-preserved anti-glaucoma medications treatment and met the severe dry eye criteria, were included in the analysis. All patients were maintained the original topical anti-glaucoma treatment. In the SH-treated group （56 eyes）, unpreserved 0.3% SH eye drops were administered with 3 times daily for 90 days. In the control group （55 eyes）, phosphate-butTered saline were administered with 3 times daily for 90 days. Ocular Surface Disease Index （OSDI） questionnaire, break-up time （BUT） test, corneal fluorescein staining, corneal and conjunctival rose Bengal staining, Schirmer test, and conjunctiva impression cytology were pertbrmed sequentially on days 0 and 91. Results： Compared with the control group, SH-treated group showed decrease in OSDI scores （Kruskal-Wallis test： H = 38.668, P 〈 0.001 ）, fluorescein and rose Bengal scores （Wilcoxon signed-ranks test： z = -3.843, P 〈 0.001, and z = 3.508, P 〈 0.001, respectively）, increase in tear fihn BUT （t-test： t - -10.994, P 〈 0.001 ） and aqueous tear production （t-test： t = -10.328, P 〈 0.001 ） on day 91. The goblet cell density was increased （t-test： t = -9.981, P 〈 0.001）, and the morphology of the conjunctival epithelium were also improved after SH treatment. Conclusions： SH significantly improved both symptoms and signs of ocular surface damage in patients with BAC-preserved anti-glaucoma medications treatment. SH could be proposed as a new attempt to reduce ocular surface toxicity, and alleviate symptoms of ocular surface damage in BAC-preserved anti-glaucoma medications treatment.
基金the National Natural Science Foundation of China(82070928 and 82171026).
文摘Objective:To investigate the anti-inflammatory,antioxidant,and goblet cell-stimulating effects of a suspension of Ophiopogon japonicus(L.f.)Ker Gawl.(O.japonicus,Mai Dong)extract combined with hyaluronic acid(HA)in the mouse model with dry eye disease(DED).Methods:A DED mouse model was induced using benzalkonium chloride(BAK),followed by treatment with O.japonicus extract-containing eye drops at varying concentrations.Experimental groups included a normal control,a DED model control,a positive control,and an O.japonicus extract-treated group.Corneal fluorescein staining and tear break-up time(TBUT)were used to assess tear film stability and ocular surface integrity.Enzyme-linked immunosorbent assay(ELISA)measured inflammatory factor levels in corneal and conjunctival tissues,whereas Western blot(WB)analyzed key antioxidant and inflammatory markers,including nuclear factor erythroid 2-related factor(2Nrf2)and heme oxygenase 1(HO-1).Periodic acid-schiff(PAS)staining and immunofluorescence were used to evaluate goblet cell density and mucin secretion.Results:O.japonicus extract significantly improved corneal damage,reduced fluorescein staining scores,prolonged TBUT,and increased tear secretion.It downregulated inflammatory markers,including interleukin-8(IL-8),interleukin-1β(IL-1β),and interferon-g(IFN-γ)while upregulating Nrf2,HO-1,and the interleukin-13(IL-13)/IFN-γ ratio,alleviating oxidative stress and inflammation.PAS staining showed increased conjunctival goblet cell density and restored mucin secretion,enhancing tear film stability.Conclusion:O.japonicus extract demonstrated significant anti-inflammatory,antioxidant,and goblet cell-stimulating effects in a DED model,with good biocompatibility and promising therapeutic potential.Future research should optimize extraction processes and validate their efficacy and safety in clinical settings.
