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PubMed1998

Comparison of the efficacy and safety of two eye gels in the treatment of dry eyes: Lacrinorm and Viscotears.

PURPOSE: To compare the efficacy and safety of two carbomer 940 eye gels in the treatment of dry eyes: Lacrinorm (also called GelTears), a recently introduced eye gel, and Viscotears (also called Vidisic or Lacrigel), used as a reference gel. The main difference between the two gels is in the preservative, respectively benzalkonium chloride and cetrimide. METHODS: A double-masked, randomised, parallel-group study was conducted in 16 centres in four European countries. A total of 179 patients suffering from aqueous-deficient dry eye were enrolled, of whom 92 were randomised to treatment with Lacrinorm and 87 to the reference gel. Gel was instilled four times a day for a period of 30 days. RESULTS: After 30 days of treatment, subjective symptoms (the combined scores of foreign body sensation, ocular dryness, burning or pain, and photophobia) had improved by 50% in the Lacrinorm group and by 45% in the reference gel group, and objective test results (break-up time, fluorescein test, Schirmer test, Lissamine Green test) by 35-36% in the Lacrinorm group and 25-45% in the reference group. The improvements were significant in both treatment groups (p < 0.001), with no significant differences between the treatment groups. Subjective local tolerability upon instillation on day 30 was rated 'good' or 'very good' by 91% of patients in both treatment groups. Adverse events were reported for 21 patients in the Lacrinorm group and 17 in the reference group, the most frequent being discomfort, blurred vision, hyperaemia, burning and itching. The frequency and descriptions of adverse events did not differ significantly between the two treatment groups. No serious adverse events were reported. CONCLUSIONS: Over the period of study, Lacrinorm eye gel was as effective and safe as Viscotears/Lacrigel in the treatment of dry eye.

Acrylic Resins↗
PubMed1998

The effect of tear substitute and silicone oil on re-epithelisation of the cornea.

PURPOSE: An animal model study was conducted to compare the effects of recurrent applications of an artificial cellulosic tear substitute and silicone oil on corneal reepithelisation. METHODS: A controlled wound was inflicted to the corneas of two groups of rabbits; one group was treated with tear substitute (5 eyes), while the other group received silicone oil (5 eyes). The left eye served as the control in both groups (10 eyes). The rate of re-epithelisation was measured at intervals of 6 h until complete wound closure was observed. After complete wound closure, the rabbits were killed and histological examinations were performed. RESULTS: The wounds of eyes treated with tear substitute closed at a statistically significant faster rate (at 24, 44, 80 h; p < 0.05) than those treated with silicone oil or the untreated eyes. At 48 h after re-epithelisation, the eyes treated with tear substitute presented a normal epithelium while the untreated and silicone-treated eyes presented an abnormally structured epithelium. CONCLUSION: This study demonstrates a favourable effect of tear substitute on corneal re-epithelisation in an animal model, in terms of both rate of re-epithelisation and histological aspects of the new epithelium.

Animals↗
PubMed2006

Tonometers and infectious risk: myth or reality? Efficacy of different disinfection regimens on tonometer tips.

PURPOSE: To evaluate the adequacy of common disinfection regimens for disposable tonometer tips and assess if disinfection of reusable prisms or the use of disposable tips is preferable. METHODS: We used disposable tonometer tips, using the same material and tip diameter of standard Goldmann tonometer prism. Strains of Pseudomonas aeruginosa, Staphylococcus aureus, Bacillus subtilisand Candida albicanswere tested according to the European standard guidelines for disinfectants test. Antimicrobial effectiveness of the following disinfection practices has been assessed: dry wipe, Minuten wipes (Alpro), soaking in 3% hydrogen peroxide, 0.5% benzalkonium chloride, and 0.5% Pantasept for 1, 5, and 15 min. All tests have been performed three times and all conditions tested in duplicate. RESULTS: Dry wiping and 1 min soak in 3% hydrogen peroxide were ineffective on all microrganisms. Minuten wipes, 1 min soak in 0.5% benzalkonium chloride or 3% hydrogen peroxide were ineffective on B. subtilis. 0.5% Pantasept soak was effective in 1 min for all microrganisms tested, whereas 3% hydrogen peroxide and 0.5% benzalkonium chloride soaks were effective when performed for at least 5 min. B. subtiliswas the most resistant organism to disinfectant regimes at 1 min time. CONCLUSIONS: Results of our study demonstrate a relative disinfection efficacy for the different evaluated regimens, provided that correct exposure times are adopted for the chosen disinfectants, a condition difficult to ensure in a busy clinic setting. We conclude that disposable prism tonometry provides a safe alternative to Goldmann tonometry.

Anti-Infective Agents, Local↗
PubMed1998

Trace analysis of benzalkonium chloride on skin by flow injection ionspray mass spectrometry-mass spectrometry.

A method for the analysis of trace-level benzalkonium chloride has been established using flow injection ionspray mass spectrometry-mass spectrometry with multiple reaction monitoring. Quantification was carried out using an external standard based on peak area summation of each benzalkonium ion (C8, C10, C12, C14, C16 and C18) in the mass spectra. The multiple reaction monitoring technique provides additional specificity for identification and quantification. The quantification linear dynamic range was found to be 5.0-100.0 ng ml-1, the correlation coefficient > 0.999, and the detection limit 1.2 ng ml-1. The method was applied to quantify benzalkonium chloride on skin, which was sampled with a D-SQUAME tape from skin surface and extracted from the tape with methanol.

Anti-Infective Agents, Local↗
PubMed1990

Column chromatographic pre-concentration of iron(III) in alloys and biological samples with 1-nitroso-2-naphthol-3,6-disulphonate and benzyldimethyltetradecylammonium-perchlorate adsorbent supported on naphthalene using atomic absorption spectrometry.

The solid ion-pair material produced from the reaction between benzyldimethyltetradecylammonium chloride (BDTA) and sodium perchlorate on naphthalene provides the basis for a simple, rapid and selective technique for pre-concentrating iron from up to 500 ml of aqueous solution. Iron reacts with disodium 1-nitroso-2-naphthol-3,6-disulphonate (Nitroso-R salt) to form a water-soluble coloured chelate anion. The iron chelate anion forms a water-insoluble, stable iron-Nitroso-R-BDTA complex on naphthalene packed in a column. Trace amounts of iron are quantitatively retained on naphthalene in the pH range 3.5-7.5 and at a flow-rate of 1-2 ml min-1. The solid mass is dissolved out from the column with 5 ml of N,N-dimethylformamide and iron is determined by means of an atomic absorption spectrometer at 248 nm. The calibration graph is linear for concentrations of iron over the range of 0.5-20 micrograms in 5 ml of final solution. The standard deviation and relative standard deviation were calculated. The detection limit of the method was 0.0196 micrograms ml-1 of iron. The sensitivity for 1% absorption was 0.072 microgram ml-1 (0.165 microgram ml-1 by direct atomic absorption spectrometry of aqueous solution). The proposed method was applied to the determination of iron in standard alloys and biological samples.

Adsorption↗
PubMed2003

Release studies of benzalkonium chloride from hydrogel in a freshwater environment.

The use of underwater optical sensors to monitor pollution and climate change processes has led to the development of robust instruments able to be deployed in lakes and seas for months at a time. However, despite this improvement in their durability they are subject to biofouling on their optical ports resulting in erroneous readings. The use of hydrogel coatings containing the cationic surfactant benzalkonium chloride (BAC) has been shown to prevent the development of biofouling for up to 12 weeks in the marine environment. In this study the use of hydrogel coatings in the freshwater environment was less successful with fouling visible at 2 weeks. In both field and laboratory studies a rapid initial loss of BAC from the hydrogel film was observed. The loss is a combination of diffusive and mass flow but the period from 12 to 50 h appeared to fit to diffusion kinetics and a diffusion coefficient of 7.3 x 10(-8) cm2 s(-1) (13 degrees C) was calculated, an order of 10 times greater than that found in seawater. Subsequently the rate of loss of the residual BAC, for which a diffusion coefficient of 5.7 x 10(-10) cm2 s(-1) (15 degrees C) was measured, was too low to prevent the early stages of biofouling.

Benzalkonium Compounds↗
PubMed1992

Natural polyamines stimulate G-proteins.

The natural polyamines spermine and spermidine, the biosynthetic precursor putrescine and their analogues cadaverine and tyramine stimulate the GTPase activity of purified GTP-binding proteins (Go/Gi) from calf brain reconstituted into phospholipid vesicles. The order of potency was spermine greater than spermidine greater than putrescine = cadaverine greater than tyramine. The physiological relevance of this observation was assessed, showing the same order of potency of polyamines in the stimulation of peritoneal and tracheal rat mast cells. The activation of rat mast cells by polyamines was inhibited by benzalkonium chloride or by a 2 h pretreatment of the cells with pertussis toxin. The increase in inositol phosphates evoked by polyamines was also inhibited by pertussis toxin. Therefore we propose that intracellular polyamines might control the basal level of second messengers and modulate extracellular signals transduced through G-protein-coupled receptors.

Animals↗
PubMed2001

Cyclosporin A exacerbates skin irritation induced by tributyltin by increasing nuclear factor kappa B activation.

In searching for pharmacologic agents able to reduce xenobiotic-induced skin irritation, we found that cyclosporine A exacerbates the skin irritation induced by tributyltin. We previously demonstrated the involvement of interleukin-1 alpha and tumor necrosis factor alpha in tributyltin-induced skin irritation. Here, we show that cyclosporine A (28 mg per kg), at a dose that results in systemic immunosuppression, potentiates tributyltin-induced skin irritation through increased tumor necrosis factor alpha production, associated with increased tributyltin-induced activation of transcription factor nuclear factor kappa B in cyclosporine-A-treated mice. On the other hand, under the same experimental conditions, cyclosporine A prevented the elicitation phase of oxazolone-induced contact allergy, but was ineffective in preventing benzalkonium-chloride-induced skin irritation. Using a murine keratinocyte cell line (HEL30) we demonstrated, also in vitro, that the cyclosporine A potentiates tributyltin-induced nuclear factor kappa B activation and cytokine production, this being preceded by an increase in cellular oxidative activity, essential for nuclear factor kappa B activation, that is time and dose (0.1-10 microM) dependent. This effect was not exclusive to tributyltin but could be extended to other mitochondrial poisons such as sodium arsenate. It has been reported that cyclosporine A binds to cyclophilins. An 18-mer antisense phosphorothioate oligodeoxynucleotide was used to target mitochondrial cyclophilin D mRNA. After 24 h exposure to the oligonucleotide, the amount of cyclophilin D in the cells was decreased by 54% as judged by Western blot analysis. Cyclophilin D suppression prevented cyclosporine A potentiation of tributyltin-induced cellular oxidative activity, indicating the key role of the binding of cyclosporine A to mitochondrial cyclophilin D in mediating this effect.

Adjuvants, Immunologic↗
PubMed1998

Effect of intracolonic benzalkonium chloride on trinitrobenzene sulphonic acid-induced colitis in the rat.

BACKGROUND: We investigated the effects of benzalkonium chloride (BAC) on trinitrobenzene sulphonic acid (TNBS)-induced colitis in rats. METHODS: TNBS was administered intrarectally before and/or after BAC treatment. In the first study, the effects of treatment with BAC 6, 12 or 24 h after TNBS were examined. In the second study, animals were treated with BAC before, after or before and after TNBS, and were examined 7 days later. The severity of colitis was assessed by macroscopic and histological scoring of the colonic damage and by determination of colonic myeloperoxidase (MPO) activity. Macrophages and CD4+ and CD8+ T cells were examined by immunohistochemistry. RESULTS: When BAC was instilled into the colon 6, 12 or 24 h after TNBS, weight loss and macroscopic and histological features of the colon were similar to that of controls (TNBS alone). In contrast, MPO activity was significantly reduced in all three groups post-treated with BAC. In the groups examined 7 days after TNBS treatment, rats post-treated with BAC exhibited increased weight gain and significantly reduced macroscopic damage and MPO activity compared to the TNBS control group. Rats pre-treated with BAC exhibited less macroscopic damage of the colon than rats receiving only TNBS, but histological damage, MPO and weight gain were unchanged from TNBS controls. Immunohistochemistry revealed that BAC pre-treatment increased the numbers of macrophages and T cells in the colon. After TNBS treatment, macrophage accumulation was evident in the colon, but T cells were scarce. However, these cells were preserved or enhanced in the colonic mucosa in TNBS-treated rats that had been pre-treated with BAC. CONCLUSIONS: Treatment with BAC, particularly after induction of colitis, produces a significant reduction in the severity of tissue injury and inflammation through mechanisms that are not fully understood.

Animals↗
PubMed1997

Immediate and short-term effects of benzalkonium chloride on the human nasal mucosa in vivo.

The in vivo effects of benzalkonium chloride, which is a preservative in most nasal sprays and drops, have been investigated in normal human volunteers. Saccharin clearance time was slightly prolonged 10 min after 0.02% benzalkonium chloride was applied, compared to that following 0.9% saline (n = 27, P = 0.04, Wilcoxon test). Sixty-five normal volunteers were randomly assigned to receive saline, fluticasone propionate aqueous nasal spray or placebo (which contained all the ingredients of fluticasone aqueous spray incl. 0.02% benzalkonium chloride, minus the fluticasone propionate) for 2 weeks, two puffs twice a day on a double-blind basis. Symptom scores, acoustic rhinometry, saccharin clearance time and ciliary beat frequency were measured immediately prior to this study and again at 2 weeks. Fifty-eight individuals completed the study with > 80% compliance. There was no significant difference between the three groups in any of the variables tested. Benzalkonium chloride causes slight prolongation of mucociliary clearance shortly after application but has no detectable effect on nasal mucosal function after 2 weeks regular use.

Adult↗
PubMed2000

A central venous catheter coated with benzalkonium chloride for the prevention of catheter-related microbial colonization.

In an attempt to overcome infections associated with central venous catheters, a new antiseptic central venous catheter coated with benzalkonium chloride on the internal and external surfaces has been developed and evaluated in a clinical trial. Patients (235) randomly received either a triple-lumen central venous catheter coated with benzalkonium chloride (117) or a polyurethane non-antiseptic catheter (118). The incidence of microbial colonization of both catheters and retained antiseptic activity of the benzalkonium chloride device following removal were determined. The benzalkonium chloride resulted in a significant reduction of the incidence of microbial colonization on both the internal and external catheter surfaces. The reduction in colonization was detected at both the intradermal (21 benzalkonium chloride catheters vs. 38 controls, P = 0.0016) and distal segments of the antiseptic-coated catheters. Following catheter removal retained activity was demonstrated in benzalkonium chloride catheters which had been in place for up to 12 days. No patients developed adverse reactions to the benzalkonium chloride catheters. The findings demonstrate that the benzalkonium chloride catheter significantly reduced the incidence of catheter-associated colonization.

Analysis of Variance↗
PubMed2000

Endocrine cells in the denervated intestine.

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.

Animals↗
PubMed2000

One explanation for the variability of the bacterial suspension test.

Disinfection kinetic studies of sodium dodecyl sulphate, benzalkonium chloride and sodium hypochlorite against Staphylococcus aureus revealed that when a higher inoculum level of Staph. aureus than normal was used (approximately 1 log higher), the efficacy of disinfection was severely attenuated. Kinetic analysis using the Hom model for experiments carried out on tests using 3 x 108 organisms ml-1 were unable to account for the large increase in disinfection power observed when smaller inoculum levels were used. Since the inoculum was the same in every way except for the numbers used, the large variations in the log reduction/time curves could not be explained by a variation in the resistance of the population to the biocide, as identical log reduction-time curves should have resulted. The level of disinfection achieved for a given concentration of biocide was found to be approximately linearly related to the cell number ml-1 of test solution and not to the log number. The variation observed is believed to occur due to intrinsic self-quenching of the biocide by the microbes during the course of the disinfection test. As the level of free biocide decreases, the rate of reaction decreases, giving the tails of the log reduction/time curves. Such intrinsic self-quenching could explain the large variations known to occur in the legally required disinfection suspension tests.

Bacteriological Techniques↗
PubMed2001

The relationships and susceptibilities of some industrial, laboratory and clinical isolates of Pseudomonas aeruginosa to some antibiotics and biocides.

AIMS: To provide evidence to support or refute the hypothesis that cross-resistance between antibiotics and biocides can occur. METHODS AND RESULTS: Fifty-five strains of Pseudomonas aeruginosa were tested for their resistance to anti-pseudomonal antibacterials. Twenty clinical, 19 industrial and 16 culture collection isolates were used. The MIC was found for the antibiotics amikacin, ceftazidime, ciprofloxacin, gentamycin, ticarcillin, tobramycin, imipenem and polymyxin B. The MIC was also found for the biocides benzalkonium chloride and chlorhexidine. The analysis of the data was based on the production of a normal distribution of the log (MIC) plots for each antimicrobial. Strains were then labelled as resistant, intermediate or sensitive based on the mean and standard deviation of the distributions. CONCLUSIONS: In general the clinical isolates were the most recalcitrant organisms, with the industrial isolates being the most sensitive. SIGNIFICANCE AND IMPACT OF THE STUDY: The work shows that antibiotic/biocide correlations do occur, especially with clinical strains. That such correlations were not found with industrial isolates suggests that the clinical environment is responsible for the correlation. We could infer that it is the selective pressure of antibiotic usage that differentiates the clinical environment from the industrial.

Animals↗
PubMed2002

Survival of Listeria monocytogenes in commercial food-processing equipment cleaning solutions and subsequent sensitivity to sanitizers and heat.

AIMS: To determine the ability of Listeria monocytogenes to survive exposure to commercial food-processing equipment cleaning solutions and subsequent treatment with sanitizers or heat. METHODS AND RESULTS: Cells of five strains of L. monocytogenes were suspended in 1% solutions of eight commercial cleaners (pH 7.1-12.5) or in water (control) and incubated at 4 degrees C for 30 min or 48 h before populations were determined by plating on tryptose phosphate agar. After exposure of cells to cleaning solutions for 30 min, populations of the most resistant strain of L. monocytogenes were reduced by < or = 1.63 log10 cfu ml(-1). In only three highly alkaline cleaning solutions (pH 11.6-12.4) were populations reduced significantly (P < or = 0.05) compared with reductions in water. After 48 h, populations were significantly higher in one cleaning solution (pH 10.4) than in water, while populations in six of the other seven cleaning solutions were reduced by > or = 4.72 log10 cfu ml(-1). Cells exposed to cleaning solutions for 30 min became sensitive to 4.0 or 6.0 mg l(-1) free chlorine and to 50 or 100 mg l(-1) benzalkonium chloride and cetylpyridinium chloride, common components of quaternary ammonium sanitizers. Cells exposed to four of the five test cleaners had D56 degrees C values less than or equal to those of the control cells. CONCLUSIONS: Listeria monocytogenes tolerates exposure to a high concentration of alkaline cleaning solutions but consequently becomes sensitized to sanitizers. SIGNIFICANCE AND IMPACT OF THE STUDY: The elimination of L. monocytogenes surviving exposure to alkaline cleaning solutions widely used for food-processing equipment is essential and the appropriate use of sanitizers for subsequent application to equipment is important in achieving this goal.

Anti-Infective Agents, Local↗