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PubMed1998

Antiviral activity of Viracea against acyclovir susceptible and acyclovir resistant strains of herpes simplex virus.

Viracea, a topical microbicide, is a blend of benzalkonium chloride and phytochemicals derived from Echinacea purpurea and is a proprietary formula from Destiny BioMediX Corp. Viracea was tested against 40 strains of herpes simplex virus (HSV): 15 strains (five HSV-1 and ten HSV-2) were resistant to acyclovir (ACV-R) and 25 strains (13 HSV-1 and 12 HSV-2) were susceptible to ACV (ACV-S). The median ED50 of Viracea for the five ACV-R strains of HSV-1 was a 1:100 dilution of the drug with a range of 1:50-1:400. The median ED50 of Viracea for the ten ACV-R strains of HSV-2 was 1:200 with a range of 1:50-1:3200. For the ACV-S strains of HSV-1 and HSV-2, the median ED50 of Viracea was 1:100 and 1:200, respectively. The cytotoxicity of Viracea was evaluated in a standard neutral red dye uptake assay in human foreskin fibroblasts. The cytotoxicity of Viracea approached only 50% at the highest concentration of the drug tested, a 1:2 dilution, indicating that Viracea is non-toxic in this cell cytotoxicity assay. Although the active component(s) in Viracea that has anti-HSV activity is not known, it appears that this extract has good antiviral activity against both ACV resistant and ACV susceptible strains of HSV-1 and HSV-2.

Acyclovir↗
PubMed2001

Adrenomedullin and proadrenomedullin N-terminal 20 peptide induce histamine release from rat peritoneal mast cell.

Adrenomedullin (ADM)-induced histamine release from rat peritoneal mast cells was investigated. We compared the ability of full-length ADM to induce histamine release to the fragments ADM-(1-25) and ADM-(22-52), as well as proadrenomedullin N-terminal 20 peptide (PAMP). ADM (10(-8) to 10(-5) M) and PAMP (10(-8) to 10(-5) M) dose-dependently increased histamine release from peritoneal mast cell preparations. The effect of ADM-(1-25) was similar to ADM, whereas ADM-(22-52) did not show any effects. These data suggest the relative importance of the ADM C-terminal fragment, which contains a six-membered ring structure. Histamine release, induced by ADM, was significantly and dose-dependently inhibited by the addition of ADM-(22-52) (10(-5) M), Ca(2+) (0.5 to 2.0 mM), and benzalkonium chloride (3 to 7 microM), a selective inhibitor of Gi type G proteins. In contrast, PAMP (10(-5) M)-induced histamine release was not inhibited by Ca(2+). These results suggest that ADM induce histamine release via a putative ADM receptor in a manner sensitive to Gi-protein function and extracellular Ca(2+) concentration, and that PAMP might produce its effect by a different mechanism than ADM.

Adrenomedullin↗
PubMed2006

[In vivo assessment of corneal epithelial toxicity of timolol with benzalkonium chloride using very-high-frequency ultrasound imaging].

PURPOSE: To assess in vivo the corneal epithelial damage caused by a topical toxic medication using a 60-MHz ultrasound device. MATERIAL: and methods: A solution of timolol with 0.01% benzalkonium chloride (BAC) was applied twice a day in the test eyes of ten rabbits, and a BAC-free solution of timolol in the control eyes, for 56 days. We used a 60-MHz ultrasound device to evaluate the epithelial damage in BAC-exposed eyes, compared to control eyes. The clinical and ultrasound examinations were performed every week, and the histological analysis at the end of the experiment. RESULTS: The clinical findings were conjunctival redness, corneal staining and instability of the tear film. In vivo VHF ultrasound revealed a thinning of the epithelium of test eyes (from 40.9+/-1,6 microm at D0 to 31.8+/-3.4 microm at D56; p=0.0006 for D0 vs D56), while the epithelium of control eyes remained unchanged. Ultrasound epithelial thickness was correlated with corneal staining (at D34 and D56; p=0.0025 and 0.0377, respectively) and histological epithelial pachymetry (p=0.0176 for control and 0.0505 for tested epithelium). Moreover, we report qualitative VHF ultrasound imaging of early epithelial damage. CONCLUSION: This new device could be very useful in ocular toxicity evaluation as a reproducible and reliable tool for multicentric clinical research.

Animals↗
PubMed1983

Surgical antiseptics.

The skin cannot be sterilized because approximately 20% of the resident flora are beyond the reach of surgical scrubs and antiseptics. The goal of surgical preparation of the skin with antiseptics is to remove transient and pathogenic microorganisms on the skin surface and to reduce the resident flora to a low level. Four antiseptics which have been popular over the past two decades are discussed. Benzalkonium chloride is somewhat unstable on the skin and is too prone to contamination to be in general use. Hexachlorophene is not recommended due to narrow spectrum and risks secondary to percutaneous absorption. The iodophors are excellent antiseptics, but recent studies raise questions about effectiveness and contamination. Chlorhexidine is a very safe and effective antiseptic. Comparison studies with chlorhexidine, hexachlorophene, and iodophors show chlorhexidine to be the most effective agent. Chlorhexidine can be toxic to the middle ear and irritating to the eyes with direct contact. Caution should be used in these areas with chlorhexidine and other antiseptics.

Anti-Infective Agents, Local↗
PubMed1995

Infection resistance of surface modified catheters with either short-lived or prolonged activity.

It has been suggested that the invasion of microbes into the catheter tract occurs mainly at the time of catheter insertion. To investigate whether the presence of an antimicrobial environment during the initial period after insertion is sufficient to reduce the risk of subsequent catheter colonization and infection, we evaluated the use of benzalkonium chloride-heparin bonded (BZK-hep) central venous catheters, which exhibit short-lived surface antimicrobial activity, using a rat subcutaneous model. Bacterial adherence on these catheters was determined, seven days after challenging the insertion site with 10(6) cfu of Staphylococcus aureus. A chlorhexidine-silver sulphadiazine impregnated catheter (Arrowg+ard), with longer lasting surface antimicrobial activity, and a hydrophilic coated catheter ('Hydrocath'), were evaluated simultaneously for comparison. Unlike Arrowg+ard antiseptic catheters, BZK-hep 'Hydrocath' and control catheters had significant bacterial adherence on their surface. Arrowg+ard catheters were colonized in 19% of the animals compared with 100% in all the other groups (P < 0.05; mean cfu cm-2: control = 1.3 x 10(6), BZK-hep = 4.3 x 10(5), Hydrocath = 2 x 10(5), Arrowg+ard = 71). Our results indicate that catheters with short-lived surface antimicrobial activity are unlikely to provide long-term protection against catheter-related infection. The efficacy of Arrowg+ard catheters may be due to the initial high rate of kill and prolonged antimicrobial activity.

Animals↗
PubMed1998

Role of antimicrobial-impregnated polymer and Teflon in the prevention of biliary stent blockage.

Biliary stent blockage and microbial colonization is a common complication associated with polyurethane stents used for the relief of bile-duct obstruction caused by benign or malignant disease. In an attempt to overcome this problem the application of a 'Teflon' (polytetrafluoroethylene) stent and an antimicrobial benzalkonium chloride (BZC) impregnated polymer were investigated. The effects of these materials on microbial colonization were compared to a polyurethane stent in vitro in broth or bile. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of BZC for three commonly isolated biliary stent pathogens, Staphylococcus epidermidis, Enterococcus faecium and Enterobacter cloacae were also determined. All the isolates were sensitive to BZC. The growth kinetics of the three organisms in broth and in human pooled bile were similar. Adherence to the BZC impregnated polymer was significantly reduced as compared to the polyurethane and Teflon stents (P < 0.05) in nutrient broth. In bile, fewer organisms attached to the Teflon as compared with the polyurethane stent (P < 0.05) for all organisms. For two of the three test organisms there was less bacterial adherence to the Teflon than to the BZC impregnated polymer. The Teflon and antimicrobial stent materials studied may prevent biliary stent blockage resulting from microbial colonization.

Anti-Infective Agents, Local↗
PubMed1998

Antimicrobial efficacy of biocides tested on skin using an ex-vivo test.

An ex-vivo test was used to evaluate the activity of antimicrobials against three microorganisms, Escherichia coli, Pseudomonas aeruginosa and Staphylococcus aureus. The ex-vivo test is a carrier test using freshly excised animal skin samples maintained in viable conditions for a short period of time. Skin samples came from a veterinary practice and were excised from either dogs or cats. The antimicrobial activity of povidone iodine, chlorhexidine diacetate, cetrimide and benzalkonium chloride was also evaluated with suspension and glass-carrier tests. Generally, the activity of the antimicrobials tested was reduced when applied to the skin surface. Apart from povidone iodine (2%) against S. aureus, the biocides investigated failed to achieve a 5 log10 reduction in bacterial titre when tested with the ex-vivo method. There was no significant difference in reduction of bacterial titres after treatment with antimicrobials between the glass-carrier and the suspension tests. Furthermore, the drying process of bacterial inoculum was less detrimental on skin than on glass surfaces. This study confirmed that the activity of a biocide tested in suspension or on an inanimate surface did not reflect its activity when tested on skin. Further development of the ex-vivo test may be useful, especially for testing the antimicrobial activity of formulations with antiseptic properties.

Animals↗
PubMed1996

Microbial contamination of antiseptics and disinfectants.

BACKGROUND: There have been a number of reports on microbial contamination of antiseptics and disinfectants. At present, however, the necessity of measures to prevent contamination do not seem to be fully appreciated. We investigated microbial contamination of antiseptics and disinfectants that are used in our hospital. METHODS: Fifty-one samples of benzalkonium chloride and chlorhexidine gluconate that were being used in the hospital were examined. Viability of the contaminants detected in these samples was also tested in the agents. Then we examined measures to prevent contamination of these agents. RESULTS: Microbial contamination was detected at 10(2) to 10(7) CFU/ml in the following samples: 6 of 23 samples of cotton balls soaked in 0.02% benzalkonium chloride kept in a canister for antisepsis and disinfection (26.1%); 7 of 13 samples of 0.02%, benzalkonium chloride or 0.02% chlorhexidine gluconate in an irrigation apparatus kept at 37 degrees C for vaginal douching (53.8%); and 9 of 15 samples of 0.02% benzalkonium chloride or 0.05% chlorhexidine gluconate for storage of suction catheters in a plastic bottle (60%). The major contaminants were Burkholderia cepacia, Pseudomonas aeruginosa, Xanthomonas maltophilia, and Pseudomonas fluorescens. The first two organisms examined grew in the agents. After improvements in the handling of the antiseptics and disinfectants, no microbial contamination was observed. CONCLUSIONS: It is necessary to check microbial contamination of diluted benzalkonium chloride and diluted chlorhexidine gluconate that are in use. Such products are not recommended as antiseptics.

Anti-Infective Agents, Local↗
PubMed2000

Fractional inhibitory concentration index of combinations of antibacterial agents against cariogenic organisms.

OBJECTIVES: To examine the inhibitory effects between paired combinations of four antibacterial agents that have been investigated in dentistry against six bacteria associated with dentinal caries. METHODS: The antibacterial agents tested were: chlorhexidine dihydrochloride, benzalkonium chloride, cetrimide and cetylpyridinium chloride. Two organisms each belonging to Streptococcus, Lactobacillus and Actinomyces species were evaluated against these agents. A checkerboard microtitration method was used to determine the minimum inhibitory concentration and fractionary inhibitory concentration (FIC) and summation operator FIC index of the paired combinations of antibacterial agents against the six species of bacteria. Appropriate controls were included. The summation operator FIC index was then used to determine if synergy, antagonism, or indifference occurred as a result of interactions between the antibacterial agents and the test organisms. RESULTS: The data from a total of 295 test results were evaluated. Using summation operator FIC values for synergy as < or = 0.5 and antagonism as > 4.0 as recommended by The American Society for Microbiology, no significant synergistic or antagonistic interactions were observed between the paired antibacterial agents when tested against selected organisms. However, a tendency for an additive antibacterial effect was observed with approximately a third of the test results. Nonetheless, no combination of antibacterial agents appeared to be superior to any other. CONCLUSIONS: According to these in vitro results, there appears to be no beneficial effect of combining the antibacterial agents against the individual cariogenic micro-organisms selected. However, it may be beneficial to use combined antibacterial agents that have a broader range of activity against an ecosystem of bacteria than using individual agents.

Actinomyces↗
PubMed2003

Myenteric denervation reduces the incidence of gastric tumors in rats.

The influence of myenteric denervation on the development of gastric tumors induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) was studied after chemical denervation of the rat stomach with benzalkonium chloride (BAC). Three groups were evaluated: control, denervated and denervated with pyloroplasty. Random bred male Wistar rats were given MNNG in drinking water (100 mg/l) for 28 weeks. After the sacrifice of animals, the stomachs were removed for morphological study. BAC reduced myenteric neurons number, increased the gastric mucosa area and decreased the adenocarcinomas number and size. This decrease was more evident when denervation was associated with pyloroplasty. These results indicate that myenteric denervation reduces the incidence of experimentally induced gastric tumors.

Animals↗
PubMed2002

No reduction with ageing of the number of myenteric neurons in benzalkonium chloride treated rats.

The number of myenteric neurons may be reduced by topical serosal application of benzalkonium chloride (BAC). We studied the effects of ageing in the population of neurons that survive after the application of BAC. Ten treated and ten control animals were killed at intervals of 2, 6, 12 and 18 months after the surgery. We performed myenteric neurons counting in serially cut histological preparations of the descending colon. The control animals revealed a continuous loss of myenteric neurons number with increasing of age. Interestingly, contrary to control animals, the BAC-treated rats presented no neuron loss with ageing at any experimental time. The reasons for their survival with ageing could be related to a neuroplasticity phenomenon.

Aging↗
PubMed1998

Morphological and functional changes after benzalkonium chloride treatment of the small intestinal Thiry-Vella loop in rats.

The aim of this work was to study the effects of benzalkonium chloride (BAC) treatment on the small intestine and its functioning in rats surgically prepared with Thiry-Vella intestinal loop. The loops were treated with either BAC, which ablated much of the myenteric plexus and extrinsic innervation, or with physiological saline (SAL). In vivo drinking experiments were performed to examine the effect on fluid intake and behavioral indices of distending the loop with a balloon. Spontaneous motility and its changes induced by acetylcholine (ACh) and histamine (His) were studied on isolated stripes in vitro. Finally, samples from the loops were examined histologically. Though reduction of the cell number was less than expected and no differences of the thickness of the muscular layer between the two groups was observed, BAC treatment altered the pattern of spontaneous activity and also the sensitivity to ACh and His in isolated stripes. In vivo distension of the SAL-treated loops reduced fluid intake and produced signs of aversivity; these effects were absent in the BAC-treated group. Our results show that despite the differences in the degree of ablation from those obtained by others, BAC treatment can be used to study the mechanisms underlying the effects of the enteral stimuli on the behavior.

Anastomosis, Surgical↗
PubMed2001

Cytotoxicity of potential ocular permeation enhancers evaluated on rabbit and human corneal epithelial cell lines.

A series of prospective ocular permeation enhancers, benzalkonium chloride (BAC), cetylpyridinium chloride (CPC), ethylenediaminetetraacetic acid (EDTA), polyoxyethylene (20) stearyl ether (PSE) and polyethoxylated castor oil (PCO) were tested for cytotoxicity on cultures of rabbit (RCE) and human (HCE) corneal epithelial cells. The cells were treated for 5,15 and 60 min with different concentrations of the test substances, in serum-free medium and in medium containing 15% foetal bovine serum (FBS). The cytotoxicity was evaluated by WST-1 test. The EC(50) values for HCE, after 15 min exposure and in the presence of FBS, indicate the following order of cytotoxicity: PSE> or =BAC>CPC>EDTA>PCO. After 1 h exposure the order of decreasing cytotoxicity was PSE> or =BAC>CPC>PCO>EDTA. In all cases the presence of FBS appeared to exert a protective effect against the cytotoxic effect.

Animals↗
PubMed1996

Validated capillary electrophoretic method for the quantitative analysis of histamine acid phosphate and/or benzalkonium chloride.

A novel capillary electrophoresis method has been developed and validated for the quantitative determination of histamine acid phosphate (HAP) and/or benzalkonium chloride (BKC). The solutes were separated using a pH 2.5 phosphate electrolyte with detection at 200 nm. Acceptable precision was obtained using internal standardisation. The method was also acceptable for determining levels of histidine which is an impurity in HAP. Profiling of BKC homologues was demonstrated for batch identity purposes. This method is used routinely and it is intended to register this method in the British Pharmacopoeia to supplement current test methods of TLC and HPLC.

Anti-Infective Agents, Local↗
PubMed2003

Poly(acrylic acid) microgels (carbopol 934)/surfactant interactions in aqueous media. Part II: Ionic surfactants.

The interaction of sodium dodecylsulfate (SDS) or benzalkonium chloride (BkCl) with carbopol microgels (0.25% (w/w)) in water was studied through pH, trasmittance, viscosity, surface tension, conductivity, fluorescence, oil solubilization, and microcalorimetry measurements. In the case of the anionic surfactant, enthalpy-driven hydrophobic absorption of SDS into carbopol microgels began when SDS concentration reached 0.05-0.08% and ended around 0.6%. These concentrations were estimated as the critical aggregation (cac) and saturation binding concentration, respectively. The hydrophobic absorption of the surfactant accompanied by its counter-ion caused carbopol microgels to swell and promoted the occurrence of bridges among several carbopol microgels. As a consequence, the consistency of the dispersions increased significantly. Above binding saturation, further addition of SDS produced a shielding effect among the anionic charges of carbopol and its dehydration, which was shown as a decrease in the viscosity of the dispersions. At low shear rates, the dispersions behaved as pseudoplastic owing to orientation of carbopol/SDS aggregates in the flow direction. Increasing shear rates caused the inter-microgel bridges to break, the water layer surrounding them to diminish, and the system to show a shear-thickening behavior. In contrast, carbopol/BkCl aggregates showed shear-thickening flow in the whole range of shear rates analyzed. Electrostatic interactions between BkCl and carbopol carboxylic groups release protons to the medium and decrease the internal osmotic pressure of the microgels. This may favor the establishment of hydrophobic interactions among surfactant tails, and induces carbopol microgels to collapse. The cac was approximately 0.01% BkCl. Saturation binding occurred at 0.3-0.5%, indicating that only 25-40mol% carboxylic groups were neutralized with BkCl. The shrinking of carbopol microgels as BkCl is absorbed prevents additional surfactant molecules from interacting with the remaining carboxylic groups. Microcalorimetry assays revealed that the aggregation process occurred with a strong gain in enthalpy.

Acrylates↗