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PubMed2005

Water purification from organic pollutants by optimized micelle-clay systems.

Removal of anionic pollutants (imazaquin, sulfentrazone, sulfosulfuron) and neutral pollutants (alachlor, acetochlor, chlorotoluron, bromacil) from water by micelles preadsorbed on montmorillonite was studied. Micelles of octadecyltrimethylammonium and benzyldimethylhexadecylammonium (BDMHDA) were used. The micelle-clay systems (1% w/w) removed 87-99% of the pollutants from their water solutions containing 1-33 mg/L of herbicide. The nature of the headgroup of the organic cation, which forms the micelles, is critical. Desorption of imazaquin and acetochlor from 0.3% (w/w) suspension of BDMHDA-clay complex after 24 h was around 7% in the range of adsorbed amounts from 0.6 to 15.3 mg/g. These results indicate rather slow rates and small extents of release of pollutants from micelle-clay complexes. Column filters (25 cm) made of a mixture of quartz sand and BDMHDA micelle-clay complex at 100:1 w/w ratio removed at least 99% of above pollutants from initial solutions containing 10 mg/L; 99.5 and 97% of sulfosulfuron and alachlor were removed from their initial solutions containing 200 and 5 microg/L, respectively. These data indicate that micelle-clay complexes are very efficient for water purification from organic contaminants.

Bentonite↗
PubMed2005

Identification of benzalkonium chloride in commercial grapefruit seed extracts.

Commercial grapefruit seed extracts (GSE) were extracted with chloroform. The solvent was evaporated, and the resulting solid was subsequently analyzed by high-performance liquid chromatography (HPLC), electrospray ionization mass spectrometry (ESI/MS), tandem mass spectrometry (ESI/MS/MS), and elemental analysis (by proton-induced X-ray emission analysis). Three major constituents were observed by HPLC and were identified as benzyldimethyldodecylammonium chloride, benzyldimethyltetradecylammonium chloride, and benzyldimethylhexadecylammonium chloride. This mixture of homologues is commonly known as benzalkonium chloride, a widely used synthetic antimicrobial ingredient used in cleaning and disinfection agents.

Benzalkonium Compounds↗
PubMed1996

Effect of benzalkonium chloride/EDTA on the ocular bioavailability of ketorolac tromethamine following ocular instillation to normal and de-epithelialized corneas of rabbits.

This study was designed to examine the effect of benzalkonium chloride/ethylenediaminetetraacetic acid (BAK/EDTA) on the ocular bioavailability (Focular) of ketorolac tromethamine after ocular instillation to normal and de-epithelialized corneas of rabbits both in vitro and in vivo. The in vitro Focular of the formulations was measured in flow-through perfusion chambers. For in vivo studies, a 35 microL dose of 0.5% ketorolac tromethamine with or without BAK/EDTA was instilled into rabbit eyes with intact or de-epithelialized corneas. At 0.5, 1, 2, 4, 6, and 8 h postdose, rabbits were euthanized, and the corneas and aqueous humor were collected from both eyes. The ketorolac concentrations from both in vivo and in vitro samples were quantified by reversed-phase high-performance liquid chromatography. The in vitro study results indicated that BAK/EDTA statistically significantly increased the Focular of ketorolac through de-epithelialized corneas but not through intact corneas. The in vivo study results showed that BAK/EDTA had no effect on the Focular of ketorolac in rabbits with intact corneas, based on the values of the area under the aqueous humor concentration versus time curves (AUC0-6h) of ketorolac. As expected, de-epithelialization of the corneas produced a faster and greater ocular absorption of ketorolac as evidenced by the smaller Tmax and larger AUC values compared to those for the intact corneas in vivo. However, BAK/EDTA decreased the ocular absorption of ketorolac in rabbits with de-epithelialized corneas. The half-lives (t 1/2) of ketorolac in corneal tissue and aqueous humor were longer in rabbits with intact corneas than those in rabbits with de-epithelialized corneas. In conclusion, the in vivo Focular of ketorolac was not altered by BAK/EDTA in rabbits with intact corneas, but it was decreased by BAK/EDTA in rabbits with de-epithelialized corneas. Therefore, the formulation with ketorolac alone may be better as a post-operative ocular analgesic.

Animals↗
PubMed1998

Adverse effects of topical antiglaucomatous medications on the conjunctiva and the lachrymal (Brit. Engl) response.

BACKGROUND: Increasing evidence indicates that long-term use of topically administered medication can induce changes in the conjunctiva and lachrymal function. METHODS: In order to evaluate changes in the conjunctiva and lachrymal response after prolonged use of topically administered antiglaucoma medications and preservatives found in antiglaucomatous medication solutions (benzalkonium chloride), we tested lachrymal function (Schirmer I., Jones, BUT, Ferning tests) and used the conjunctival impression cytology technique. MATERIALS: A group of patients with primary open angle glaucoma (POAG) receiving topical antiglaucomatous medication were recruited. A second group received only preservative instillations while a control group was formed of similarly aged subjects with no eye disease and was given topical or systemic medical therapy. Excluded from the trial were patients with a history of external eye disease or who had received conjunctival surgery. RESULTS: Tear secretion was reduced against that of the control group in those subjects who received protracted administration of antiglaucomatous eyedrops (timolol and/or pilocarpine). A statistically significant degree of conjunctival metaplasia was associated with long-term use of topical medication. The subjective symptoms reported by those patients receiving chronic topical antiglaucomatous therapy and the objective observations on them were found to be proportional to the observed tearing response. Changes were more pronounced in subjects who received only benzalkonium chloride. CONCLUSION: Our study results suggest that long-term use of antiglaucoma medication induces changes in both tear film and conjunctival surface. Such changes may be related to the medication or the duration of treatment, but may also be due to the preservatives used in the commercial product.

Adrenergic beta-Antagonists↗
PubMed2001

The mucosal toxicity of different benzalkonium chloride analogues evaluated with an alternative test using slugs.

PURPOSE: The objective of this study was to evaluate the mucosal toxicity of different benzalkonium chloride (BAC) analogues using slugs as the alternative test organism. METHODS: The effect of different BAC analogues on the mucosal tissue of slugs was determined from the protein, lactate dehydrogenase, and alkaline phosphatase released from the foot mucosa after treatment. Additionally, mucus production and reduction in body weight of the slugs were measured. The eye irritation potency of the molecules was evaluated with the Bovine Corneal Opacity and Permeability (BCOP) assay. The antimicrobial activity of the different BAC analogues was also assessed. RESULTS: All BAC analogues induced severe damage to the mucosal epithelium of the slugs, and the irritation increased with decreasing alkyl chain length: BAC-C16 < BAC-C14 < BAC-C12 approximately BAC-mix. A similar ranking was obtained with the BCOP assay for eye irritation. The relative order of activities among the three BAC analogues was the same, i.e., BAC-C14 > or = BAC-C16 > BAC-C12. The BAC-C14 exhibited higher activity than the BAC-mix. CONCLUSIONS: The toxicity and activity of BAC analogues depend on the alkyl chain length. The use of BAC-C14 as a conservative agent in pharmaceutical preparations instead of the BAC-mix should be considered.

Alkaline Phosphatase↗
PubMed1991

Formulation influence on conjunctival penetration of four beta blockers in the pigmented rabbit: a comparison with corneal penetration.

The objective of this study was to compare the influence of pH, tonicity, benzalkonium chloride, and EDTA on the conjunctival and corneal penetration of four beta blockers--atenolol, timolol, levobunolol, and betaxolol. Drug penetration was evaluated using the isolated pigmented rabbit conjunctiva and cornea in the modified Ussing chamber. The conjunctiva was more permeable than the cornea to all four beta blockers. Formulation changes caused larger changes in corneal than in conjunctival drug penetration, especially for the hydrophilic beta blockers, atenolol and timolol. Raising the solution pH to 8.4 caused the largest increase in corneal penetration for all drugs except atenolol. This increase was greater than that obtained by removing the corneal epithelium. The same formulation also increased conjunctival drug penetration, although to a lesser extent. In the case of timolol, the formulation changes evaluated brought about similar changes in its ocular and systemic absorption with good in vitro-in vivo correlations. The above findings indicate that in making formulation changes to maximize corneal drug penetration, it is necessary to evaluate possible changes in conjunctival drug penetration, hence systemic absorption. Moreover, because the conjunctiva plays an active role in the noncorneal route of ocular drug absorption, the relative contribution of the noncorneal to the corneal routes to ocular drug absorption may also be altered by formulation changes.

Animals↗
PubMed1999

Peptidoleukotriene (PLT) release and absorption from the airways of the isolated perfused guinea pig lung following chemical and antigenic challenge.

PURPOSE: To study the release and absorption of peptidoleukotrienes (PLTs) from the airways of the guinea pig lung following calcium ionophore A23187 (CI), benzalkonium chloride (BAC), ethylene diamine tetra-acetic acid (EDTA) or ovalbumin (OA) challenge. METHODS: PLT C4/D4/E4 were quantified in the perfusate of the isolated perfused guinea pig lung (IPGPL) following intratracheal administration of CI, BAC, EDTA or OA in different doses. The formation and airway-to-perfusate transfer kinetics of PLTs were analyzed by fitting mean data for cumulative PLT in perfusate vs. time to an A-->B-->C first-order release and transfer model, with dose-dependent transfer rate constants. RESULTS: CI induced apparent first order release of PLTs with a t1/2 approximately equal to 1.2 minutes. The amount of PLT released was CI dose-dependent, as was the airway-to-perfusate transfer rate constant. These reached maxima of 0.254 microgram and 0.0557 min.-1, respectively, around a CI dose of 100 micrograms. In OA-sensitized IPGPL preparations, OA induced a similar dose-dependent release of PLTs, although the rates of PLT release were much greater and more variable than those seen with CI. In OA sensitized IPGPL preparations, at an OA dose of 1000 micrograms, the maximum amount of PLT released was 0.289 micrograms and the maximal airway-to-perfusate transfer rate constant was 0.0229 min-1. BAC and EDTA failed to induce quantifiable PLT release from the airways. CONCLUSIONS: Rapid release of the inflammatory mediators, PLT C4/D4/E4, could be induced in the unsensitized IPGPL by CI, and in the sensitized IPGPL by OA. Transfer into perfusate occurred in both cases with dose-dependent t1/2 ranging from 12.4 through 57.8 minutes.

Absorption↗
PubMed2002

Effects of myenteric denervation on gastric epithelial cells and gastric emptying.

The influence of myenteric denervation on gastric emptying and epithelial cell population was studied by chemical lesion of myenteric neurons of rat stomach with benzalkonium chloride. Three groups were evaluated: denervated, denervated with pyloroplasty, and control. After three months, the animals were submitted to functional (gastric emptying of liquids) and morphological (neuronal counting; mucosal area, height, and volume; mucous, chief, and parietal cell population; parietal cell area; and gastrin-G and somatostatin-D cell population) studies. After benzalkonium chloride treatment, there was significant delay in gastric emptying of liquids and an increase in mucosal area of all gastric portions, in antral mucosal volume, in parietal cell area, and gastrin-G cell and somatostatin-D cell populations. These changes did not occur when denervation was combined with pyloroplasty, indicating that after denervation, gastric distension and stasis are the major stimuli for parietal cell hypertrophy and G and D cell hyperplasia

Animals↗
PubMed2002

Modified method for evaluation of plasma membrane integrity in eukaryotic cell.

We propose a method for evaluation of the number of viable cells by the content of bromcresol purple dye absorbed by dead cells from the incubation medium. Myramistin was used as a pore-forming agent. The number of live cells in yeast suspension inversely correlated with the percentage of dye absorbed by cells. The method is simple and requires no special equipment. The effect of myramistin on Candida albicans and Malassezia sympodialis cells and on epitheliocytes was evaluated. Two-hour treatment with myramistin in a concentration commonly used in clinical practice (100 mug/ml) decreased the number of viable cells by 2 and 1 order of magnitude, respectively. Epitheliocytes under the same conditions absorbed approximately the same mount of the dye as Candida cells.

Benzalkonium Compounds↗
PubMed1998

Changes in muscularis externa of rat small intestine after myenteric ablation with benzalkonium chloride: electron microscopic and morphometric study.

The influence of the intrinsic innervation on the muscularis externa of the rat small intestine was studied by chemical ablation of the myenteric plexus with benzalkonium chloride (BAC). The resulting severe hypertrophy (cell hypertrophy of 96-133% and hyperplasia) differs from working hypertrophy by the distribution and degree of muscle thickening and by characteristics of the extracellular matrix: narrowing of muscle interspaces of 43%; lack of increased collagen; changes in the ratio of interstitial cells of Cajal (ICCs) to fibroblasts from 1.6:1 to 0.8:1 with no numerical decrease in either type of cell; decreased interconnections of ICCs to muscles and nerves due to deformed ICCs; a 197% increase in vascularization (capillaries, venules) and lymphatics in both muscle layers and in the myenteric plexus cleft, possibly initiated by release of fibroblast growth factor from myelin fragmentation after nerve damage; and increased macrophages, plasma cells, monocytes and mast cells in the myenteric plexus cleft. These all signify the neural influence on the morphodifferentiation of the muscularis externa in concert with the extracellular matrix components.

Animals↗
PubMed2002

Cutaneous field stimulation of sensory nerve fibers reduces itch without affecting contact dermatitis.

BACKGROUND: A new technique, cutaneous field stimulation (CFS), which activates electrically unmyelinated C-fibers, is used to treat localized itch. Its action is similar to that of capsaicin, the pungent agent in hot peppers, which enhances delayed allergic reactions. The aim of the study was to investigate how experimental contact dermatitis responds to CFS. METHODS: Twelve patients with contact dermatitis in response to nickel were treated by CFS for 1 h each for four consecutive days. A flexible plate containing electrodes was applied to a test area on the upper arm and was stimulated by a constant current (0.8 mA). On the fifth day, patients were provoked by epicutaneous application of nickel sulfate (allergic contact dermatitis) and benzalkonium chloride (irritant contact dermatitis), and by intradermal tuberculin (delayed immunologic reaction). Twelve other patients with IgE-mediated allergy were treated by CFS on the lower arm for 1 h and were then pricked with histamine and allergen extracts (wheal volume was measured) and were tested using benzoic acid (nonimmunologic contact urticaria; closed test). Ten of these patients were also treated by CFS for four days, and experiments were performed on the fifth day. RESULTS: Test reactions to nickel, benzalkonium, and tuberculin were found to be unaffected by CFS treatment. Although allergic prick test reactions were enhanced (by 28%) after a single CFS treatment, the associated itch was significantly reduced both after single and repeated CFS treatments (by 65% and 38%, respectively). CONCLUSIONS: Repeated use of CFS to reduce itch has no adverse effects on contact dermatitis.

Administration, Cutaneous↗
PubMed2002

Topical application of benzalkonium chloride to the stomach serosa increases gastric emptying time, acid secretion, serum gastrin and size of the mucosa.

AIM: In the present study we evaluated the effects of gastric myenteric denervation using benzalkonium chloride (BAC) on the time for gastric emptying, as well as gastric secretion, and mucosal epithelial cell size and population in rats. METHODS AND RESULTS: Wistar rats were treated with topical serosal application of BAC to the stomach. Control animals received saline. Ninety days after surgery, gastric emptying time, gastric acid secretion and serum gastrin levels were studied. Next, the animals were sacrificed and the stomachs were removed, fixed in formalin and histologically processed for histomorphometry of the height, area and volume of the glandular portion, and volume and population of mucous, chief, parietal, G- and labelled cells. BAC animals showed a significant delay in gastric emptying and an increase in gastric acid secretion and serum gastrin levels. These animals also presented a significant reduction of myenteric neuron number, hypertrophy of parietal and chief cells, hyperplasia of G cells and an increase in the gastric mucosa area. CONCLUSION: The absence of the myenteric plexus seems to protect the stomach from the hyperplastic effects of hypergastrinemia. Gastric food stasis may act as a factor triggering morphological and functional alterations of the gastric epithelium. Although gastric food stasis is a common finding in medical practice, its physiopathological consequences are poorly understood and have not been frequently discussed in the literature.

Animals↗
PubMed2000

Benzalkonium chloride neutralizes the irritant effect of sodium dodecyl sulfate.

When benzalkonium chloride (BKC), a cationic surfactant, is added to sodium dodecyl sulfate (SDS), an anionic surfactant, and used in patch testing, on the basis of their known physicochemical interaction, it is possible to predict that there will be a tendency towards a reduction in the expected irritant response when compared to SDS alone. The aim of this study was to investigate whether BKC could reduce the irritant response to SDS when applied after the SDS exposure. 54 non-atopic adult volunteers were recruited for the study. 20% SDS was applied for 2 h under occlusion. 1% BKC was then applied to the same site. Various controls, including SDS application followed by water for 2 h, were included. The irritant reaction was assessed at 24 h and 48 h. 40 of the 54 subjects had some reaction when SDS was applied for 2 h followed by either benzalkonium chloride or water control under occlusion. In comparison to water control, where BKC was applied after SDS, 20 of the 40 responders had a weaker reaction but only 4 had a stronger response. This study shows that BKC applied to skin exposed to SDS attenuates the resulting irritant reaction.

Adult↗
PubMed2002

Enhancement of transmucosal permeation of cyclosporine by benzalkonium chloride.

OBJECTIVES: Permeation of cyclosporin A (CsA) through intact and de-epithelialized human vaginal mucosa in the presence and absence of benzalkonium chloride (BZCl) was tested. MATERIALS AND METHODS: Human vaginal mucosa (snap-frozen in liquid nitrogen, stored at -85 degrees C) had been used for permeability experiments. CsA permeation through thawed frozen intact and de-epithelialized vaginal mucosa was determined using a flow-through diffusion apparatus (20 degrees C, 24 h). Flux rates for CsA across these two mucosae were determined in the presence and absence of 0.01% BZCl. ANOVA and Duncan's multiple range test were used to test for steady-state and an unpaired t-test with Welch's correction was used to test for differences between the mean flux values at each time point (significance level of 5%). A piece of thawed tissue from each patient, before and after de-epithelialization, was placed in formalin and histologically examined. RESULTS: Flux rates of CsA across intact vaginal mucosa tended to increase by 28-46% in the presence of 0.01% BZCl, and CsA across de-epithelialized mucosa by approximately 28%. The latter differences were statistically significantly higher after 10 h. Flux rates across de-epithelialized mucosa were 52-140% higher in the presence of 0.01% BZCl (statistically significantly higher after 12 h). CONCLUSIONS: The permeation of CsA through intact and de-epithelialized human vaginal mucosa can be enhanced by 0.01% BZCl.

Adult↗