Effects of benzalkonium chloride on growth and survival of Chang conjunctival cells.
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PURPOSE: The aim of this study was to investigate the action of benzalkonium chloride (BAC), used as a preservative in most ophthalmic topical solutions, on epithelial conjunctival cells in vitro. METHODS: A continuous human conjunctival cell line (Wong-Kilbourne derivative of Chang conjunctiva) was exposed to BAC solutions at various concentrations (0.1%-0.0001%) during a period of 10 minutes. Cells were examined before treatment and 3, 24, 48, and 72 hours later, after reexposure to normal cell culture conditions. Cell number and viability were assessed with crystal violet and 3-(4,5-dimethylthiazol-2yl)-2,5-diphenyl tetrazolium bromide colorimetric assays. The expression of the apoptotic marker Apo 2.7, nuclear antigen p53, membrane proteins Fas and Fas ligand, and DNA content was studied by flow cytometry. Morphologic aspects of cell nuclei were analyzed on slides with a nucleic acid-specific dye, 4',6'-diamidino-2-phenylindole dihydrochloride. Cytoskeleton was labeled with a monoclonal anti-pancytokeratin antibody. In addition, apoptosis was measured by DNA electrophoresis assays in agarose gel. RESULTS: Cell exposure to 0.1% and 0.05% BAC induced cell lysis immediately after treatment. All cells (100%) treated with 0.01% BAC died in a delayed manner within 24 hours, with most of the characteristics of apoptosis (chromatin condensation and DNA fragmentation, reduction in cell volume, expression of the apoptotic marker Apo 2.7, and apoptotic changes in DNA content). Aliquots of 0.005%, 0.001%, 0.0005%, and 0.0001% BAC induced growth arrest and apoptotic cell death in a dose-dependent manner between 24 and 72 hours after treatment. The expressions of Fas and p53 did not vary after BAC treatment. Fas ligand was always negative. CONCLUSIONS: These results suggest that BAC induces cell growth arrest and death at a concentration as low as 0.0001%. The mode of BAC-induced cell death is dose-dependent. Cells die by necrosis after BAC treatment at high concentrations and by apoptosis if low concentrations of BAC are applied. This new aspect of in vitro toxicity of BAC could in part explain some ocular surface disorders observed in patients undergoing long-term topical treatments with preservative-containing drugs. (+info)
Cluster of postinjection abscesses related to corticosteroid injections and use of benzalkonium chloride.
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Benzalkonium chloride (BC) is an unreliable disinfectant. A matched case-control study and environmental investigation were conducted to determine the cause of and risk factors for a cluster of postinjection abscesses at a private medical clinic where BC was used as a disinfectant. Twenty-eight case-patients who had an abscess at the injection site were matched with 126 control patients who had received an intramuscular injection at the clinic on the same day. Risk factors for abscess development in a multivariable logistic model were corticosteroid injection and being female. All case-patients had received a corticosteroid injection from a multidose vial. Cultures of abscesses from 20 of 23 case-patients grew Pseudomonas aeruginosa. Cultures of BC prepared at the clinic also grew P aeruginosa, suggesting that BC was the source of infection. Injection site cleaning with BC did not appear to be the route of infection since use of BC at the time of injection was not associated with abscess development. A more likely route of infection was injection of contaminated corticosteroid from multidose vials that could have been inoculated with pseudomonads via needle puncture after vial septa were wiped with contaminated BC. Benzalkonium chloride should not be used to clean injection vial septa or injection sites. (+info)
Using of thin-layer chromatography for identification and quantitative determination of benzalkonium chloride in eye drops.
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Conditions for thin-layer chromatographic separation of components (therapeutic and auxiliary substances) in selected eye drops have been established and next used for the densitometric determination of benzalkonium chloride content in the drugs. (+info)
Safety and acceptability of vaginal disinfection with benzalkonium chloride in HIV infected pregnant women in west Africa: ANRS 049b phase II randomized, double blinded placebo controlled trial. DITRAME Study Group.
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OBJECTIVES: To study the tolerance and acceptability in Africa of a perinatal intervention to prevent vertical HIV transmission using benzalkonium chloride disinfection. DESIGN: A randomized, double blinded phase II trial. SETTING: Prenatal care units in Abidjan (Cote d'Ivoire) and Bobo-Dioulasso (Burkina Faso). PATIENTS: Women accepting testing and counselling who were seropositive for HIV-1 and under 37 weeks of pregnancy were eligible. A total of 108 women (54 in each group) enrolled from November 1996 to April 1997, with their informed consent. INTERVENTION: Women self administered daily a vaginal suppository of 1% benzalkonium chloride or matched placebo from 36 weeks of pregnancy, and a single intrapartum dose. The neonate was bathed with 1% benzalkonium chloride solution or placebo within 30 minutes after birth. MAIN OUTCOME MEASURES: Adverse events were recorded weekly, with a questionnaire and speculum examination in women through delivery, and examination of the neonate through day 30. The incidence of genital signs and symptoms in the women and cutaneous or ophthalmological events in newborns were compared between groups on an intent to treat basis. RESULTS: The median duration of prepartum treatment was 21 days (range 0-87 days). Compliance was 87% for prepartum and 69% for intrapartum treatment, and 88% for the neonatal bath, without differences between the two groups. In women, the most frequent event was leucorrhoea; the incidence of adverse events did not differ between treatment groups. In children, the incidence of dermatitis and conjunctivitis did not differ between the benzalkonium chloride and placebo groups (p = 0.16 and p = 0.29, respectively). CONCLUSION: Vaginal disinfection with benzalkonium chloride is a feasible and well tolerated intervention in west Africa. Its efficacy in preventing vertical HIV transmission remains to be demonstrated. (+info)
Emergence of resistance to biocides during differentiation of Acanthamoeba castellanii.
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A synchronous encystment method was used to study the order of development of resistance of Acanthamoeba castellanii to a range of biocides. The emerging resistance during encystation to short-term exposure to the minimum amoebicidal concentrations of each biocide tested was recorded during the first 36 h of the differentiation process. Hydrochloric acid and moist heat were tested as possible resistance markers. Development of the acid-insoluble, proteincontaining, ectocyst wall and the cellulose endocyst wall was followed by quantification of the acid- and alkali-insoluble residues of cell samples removed from synchronous encystment cultures up to 36 h. Resistance to chemical agents (polyhexamethylene biguanide, benzalkonium chloride, propamidine isethionate, pentamidine isethionate, dibromopropamidine isethionate, hydrogen peroxide) and to moist heat was seen to develop between 14 and 24 h after trophozoites were inoculated into the encystment media. Resistance to hydrochloric acid developed between 0 and 2 h and to chlorhexidine diacetate between 24 and 36 h. Levels of acid-insoluble residues began to increase after 8 h and alkali-insoluble residues (cellulose) were detected after 16 h and coincided with the emergence of resistance to all the agents tested except hydrochloric acid. The results suggest that resistance to the biocides tested probably results largely from the physical barrier of the cyst walls rather than as a consequence of a metabolically dormant cyst. (+info)
Endocrine cells in the denervated intestine.
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This study deals with the effects of myenteric denervation of the proximal jejunum on endocrine cell population of the crypt-villus unit, 5 months after treatment with benzalkonium chloride (BAC). Male Wistar albino rats weighing on average 100 g were allocated to two groups: the BAC group - the proximal jejunal serosa was treated with 2 mM BAC for 30 min, and the control group - treated with saline solution (0,9% NaCl). There was a significant reduction in neurone number in the jejunal myenteric plexus of the BAC group and the endocrine cell population (serotoninergic and argyrophilic cells) was significantly increased in this intestine segment. In conclusion, the present findings provide further evidence that the myenteric denervation induced by BAC may lead to the development of a local imbalance of the neurotransmitters, with a consequent induction of enteroendocrine cell (argyrophilic and serotoninergic cells) hyperplasia in the crypt and villus. (+info)
Low sensitivity of Listeria monocytogenes to quaternary ammonium compounds.
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Ninety-seven epidemiologically unrelated strains of Listeria monocytogenes were investigated for their sensitivities to quaternary ammonium compounds (benzalkonium chloride and cetrimide). The MICs for seven serogroup 1/2 strains were high. Three came from the environment and four came from food; none were isolated from human or animal samples. All 97 strains carried the mdrL gene, which encodes a multidrug efflux pump, and the orfA gene, a putative transcriptional repressor of mdrL. The absence of plasmids in four of the seven resistant strains and the conservation of resistance after plasmid curing suggested that the resistance genes are not plasmid borne. Moreover, PCR amplification and Southern blot hybridization experiments failed to find genes phylogenetically related to the qacA and smr genes, encoding multidrug efflux systems previously described for the genus Staphylococcus. The high association between nontypeability by phages and the loss of sensitivity to quaternary ammonium compounds are suggestive of an intrinsic resistance due to modifications in the cell wall. (+info)
In vitro inactivation of Chlamydia trachomatis and of a panel of DNA (HSV-2, CMV, adenovirus, BK virus) and RNA (RSV, enterovirus) viruses by the spermicide benzalkonium chloride.
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Kinetics of inactivation by the detergent spermicide benzalkonium chloride (BZK) of Chlamydia trachomatis and of a panel of DNA viruses [herpes simplex virus hominis type 2 (HSV-2), cytomegalovirus (CMV), adenovirus (ADV) and BK virus (BKV)] and RNA [respiratory syncytial virus (RSV) and enterovirus (ENV)] were established in accordance with a standardized in vitro protocol. After a 5 min incubation, inactivation of >95% of HSV-2 and CMV was obtained at a concentration of 0.0025% (w/v) (25 Ig/L); concentrations as low as 0.0005%, 0.0050% and 0.0125%, induced a 3.0 log10 reduction in infectivity of HSV-2 and CMV, RSV and ADV, respectively. After a 60 min incubation, concentrations of 0.0125% and 0.050% provided a 3.0 log10 reduction in infectivity of ENV and BKV, respectively. These features indicate that sensitivity to BZK was very high (HSV-2 and CMV) or high (RSV) for enveloped viruses, intermediate (ADV) or low (ENV and BKV) for non-enveloped viruses. Furthermore, BZK had marked antichlamydial activity, showing >99% killing after only a 1 min incubation at a concentration of 0.00125%. BZK demonstrates potent in vitro activity against the majority of microorganisms causing sexually transmitted infectious diseases, including those acting as major genital cofactors of human immunodeficiency virus transmission. These attributes qualify BZK as a particularly attractive candidate for microbicide development. (+info)