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PubMed1995

Ophthalmic preservatives as absorption promoters for ocular drug delivery.

The effects of ophthalmic preservatives on the drug permeability through isolated ocular membranes of albino rabbits were investigated using a two-chamber glass diffusion cell. Tilisolol and fluorescein isothiocyanate (FITC)-dextrans (average molecular weights 4400 and 9400 Da; FD-4 and FD-10, respectively) were used as model penetrants of ophthalmic beta-blockers and peptide drugs. Preservatives significantly enhanced the corneal penetration of not only tilisolol but also FITC-dextrans. Especially, benzalkonium chloride increased the corneal permeability of FD-4 and FD-10 by 28.8 and 37.1 times, respectively. These results indicate the usefulness of ophthalmic preservatives as absorption promoters for the ocular delivery of beta-blockers and hydrophilic macromolecules. Preservatives also enhanced the conjunctival permeability of tilisolol, FD-4 and FD-10. The promoting effect of preservatives on the conjunctival drug penetration was smaller than that on the corneal one. Preservative increased the ratio of corneal to conjunctival permeability of tilisolol, FD-4 and FD-10. The different responses of corneal and conjunctival drug penetrations to ophthalmic preservatives may be useful to control the extent and pathway for the ocular and systemic absorptions of instilled drugs.

Absorption↗
PubMed2003

Interplay between nitric oxide and vasoactive intestinal polypeptide in inducing fluid secretion in rat jejunum.

Nitric oxide (NO) and vasoactive intestinal polypeptide (VIP) interact in the regulation of neuromuscular function in the gut. They are also potent intestinal secretogogues that coexist in the enteric nervous system. The aims of this study were: (1) to investigate the interaction between NO and VIP in inducing fluid secretion in the rat jejunum, and (2) to determine whether the NO effect on intestinal fluid movement is neurally mediated. The single pass perfusion technique was used to study fluid movement in a 25 cm segment of rat jejunum in vivo. A solution containing 20 mM L-arginine, a NO precursor, was perfused into the segment. The effect of the NO synthase inhibitors (L-NAME and L-nitroindazole (L-NI)) and the VIP antagonist ([4Cl-D-Phe6,Leu17]VIP (VIPa)) on L-arginine-induced changes in fluid movement, expressed as microl min(-1) (g dry intestinal weight)(-1), was determined. In addition, the effect of neuronal blockade by tetrodotoxin (TTX) and ablation of the myenteric plexus by benzalkonium chloride (BAC) was studied. In parallel groups of rats, the effect of L-NAME and L-NI on VIP-induced intestinal fluid secretion was also examined. Basal fluid absorption in control rats was (median (interquartile range)) 65 (45-78). L-Arginine induced a significant fluid secretion (-14 (-20 to -5); P<0.01). This effect was reversed completely by L-NAME (60 (36-65); P<0.01) and L-NI (46 (39-75); P<0.01) and partially by VIPa (37 (14-47); P<0.01). TTX and BAC partially inhibited the effect of L-arginine (22 (15-32) and 15 (10-26), respectively; P<0.05). The effect of VIP on fluid movement (-23 (-26 to -14)) was partially reversed by L-NAME (24 (8.4-35.5); P<0.01) and L-NI (29 (4-44); P<0.01). The inhibition of VIP or NO synthase prevented L-arginine- and VIP-induced intestinal fluid secretion through a neural mechanism. The data suggest that NO enhances the release of VIP from nerve terminals and vice versa. Subsequently, each potentiates the other's effect in inducing intestinal fluid secretion.

Animals↗
PubMed1993

[In vitro induction of chlorhexidine- and benzalkonium-resistance in clinically isolated Pseudomonas aeruginosa].

A study was made on the MIC distributions of chlorhexidine and benzalkonium chloride against clinically isolated 178 strains of Pseudomonas aeruginosa to find out the existence of strains resistant to those disinfectants and also on the in vitro induction of resistance to both drugs. The MIC of chlorhexidine gluconate was found to be distributed from 78 to 625 micrograms/ml with a single peak at 312 micrograms/ml. All 178 strains of clinical isolates were sensitive to chlorhexidine and none could be induced to become chlorhexidine resistant in vitro, suggesting that P. aeruginosa can not easily acquire chlorhexidine resistance. On the other hand, the MIC of benzalkonium chloride was distributed in two peaks; one peak was benzalkonium sensitive at 625 micrograms/ml (150 strains/178 strains: 84.3%) and the another peak was benzalkonium resistant at 5,000 micrograms/ml (28 strains/178 strains; 15.7%). Six (4.0%) of the 150 benzalkonium sensitive strains acquired benzalkonium resistance by in vitro induction of resistance; the MIC of 5 strains increased from 625 micrograms/ml to 2,500 micrograms/ml and that of the residual 1 strain increased from 312 micrograms/ml to 1,250 micrograms/ml. However, no change of MIC was observed in 28 benzalkonium-resistant strains of clinically isolated P. aeruginosa by in vitro resistance induction. Strains with MIC more than 5,000 micrograms/ml could not be obtained at all. The results suggest that the benzalkonium resistance can be introduced in P. aeruginosa whereas the resistance-acquiring rate is low. These results suggest that chlorhexidine gluconate is the first choice for prevention of Pseudomonas infection in the hospital and benzalkonium is also useful in 0.5% solution is used.

Aerosols↗
PubMed1999

[Preventive effect of postoperative disinfection of endoscope on bacterial adhesion to endoscope].

We took culture of throat swab from 77 subjects who were negative for infection of HBV, HCV, HIV and syphilis infection before and after endoscopy. Moreover, the existence of bacterium including Helicobacter pylori at overcoat of endoscopic instrument was investigated right after examination and after disinfection of endoscope. Povidoneiodine, 70% alcohol and 1% benzalkonium chloride was used as a disinfectant for endoscope, and it took less than 10 minutes to wash by hand to disinfection. alpha-haemolytic streptococci, Staphylococcus epidermids, Escherichia coli, Staphylococcus aureus, Klebsiella pneumoniae, Enterococcus faecalis, Candida, Pseudomonas aeruginosa and MRSA were cultured in throat swab. The rate of adhesion of bacterium especially such as Candida, K. pneumoniae and S. epidermids to endoscope was considerably high. 23 of 77 subjects had H. pylori infection, and the adhesion of H. pylori to endoscope was found to be 65.2% of the subjects. On the contrast, no bacterium was detected from the endoscopic instrument after careful disinfection. These findings stress the importance of postoperative disinfection of the endoscope to prevent the chance to acquire bacterial infection.

2-Propanol↗
PubMed2003

[Cytotoxic effect of antiseptics: comparison In vitro. In vivo examination of strong acidic electrolyzed water, povidone-iodine, chlorhexidine and benzalkonium chloride].

Cytotoxic effect and guinea pig wound cure stage, pus fabrication presence in infected wound were compared with strong acidic electrolyzed water (AcEW) and povidone-iodine solution (PVP-I), chlorhexidine (CHG) and benzalkonium chloride (BAC). It gave the following results: In a cytotoxic test, the toxicity was recognized in 0.1%-0.01% PVP-I, in 0.0002-0.0004% CHG, in 10-0.1 micrograms/ml BAC, but there was no toxicity in AcEW. By a guinea pig wound cure process, no significance was recognized between each pharmaceutical agent in epidermal cell migration, but by an inflammation locus area, the significance was considerable in comparison with no-treatment. The pyopoiesis of P. aeruginosa infected wound was recognized in a ratio of 38.2% physiological saline, 27.3% CHG, 20.6% PVP-I and 12.1% AcEW. When pollution locus includes an infection image of bacteria, while draining AcEW instead of physiological saline, disinfection, indication was expected, and, as for the disorder in cure stage. I do not agree with that mentioned above. As for AcEW, availability by organism use was recognized for the cytotoxic effect of antiseptic instead of action of acceleration for wound cure.

Animals↗
PubMed2006

Adaptive resistance and differential protein expression of Salmonella enterica serovar Enteritidis biofilms exposed to benzalkonium chloride.

The development of adaptive resistance of Salmonella enterica serovar Enteritidis ATCC 4931 biofilms following exposure to benzalkonium chloride (BC) either continuously (1 microg ml(-1)) or intermittently (10 microg ml(-1) for 10 min daily) was examined. Biofilms adapted to BC over a 144-h period could survive a normally lethal BC challenge (500 microg ml(-1) for 10 min) and then regrow, as determined by increases in biofilm thickness, total biomass, and the ratio of the viable biomass to the nonviable biomass. Exposure of untreated control biofilms to the lethal BC challenge resulted in biofilm erosion and cell death. Proteins found to be up-regulated following BC adaptation were those involved in energy metabolism (TpiA and Eno), amino acid and protein biosynthesis (WrbA, TrxA, RplL, Tsf, Tuf, DsbA, and RpoZ), nutrient binding (FruB), adaptation (CspA), detoxification (Tpx, SodB, and a probable peroxidase), and degradation of 1,2-propanediol (PduJ and PduA). A putative universal stress protein (YnaF) was also found to be up-regulated. Proteins involved in proteolysis (DegQ), cell envelope formation (RfbH), adaptation (UspA), heat shock response (DnaK), and broad regulatory functions (Hns) were found to be down-regulated following adaptation. An overall increase in cellular protein biosynthesis was deduced from the significant up-regulation of ribosomal subunit proteins, translation elongation factors, and amino acid biosynthesis protein and down-regulation of serine endoprotease. The cold shock response, stress response, and detoxification are suggested to play roles in the adaptive resistance of Salmonella serovar Enteritidis biofilms to BC.

Adaptation, Physiological↗
PubMed2002

Effects of chemical and physical agents on viability and infectivity of Encephalitozoon intestinalis determined by cell culture and flow cytometry.

We combined tissue culture and flow cytometry to assess the activities of various temperatures, chemicals, and disinfectants on the viability and infectivity of spores of Encephalitozoon intestinalis. Surfanios and benzalkonium chloride, disinfectants currently used in the hospital, were remarkably efficient in destroying spore viability and infectivity.

Animals↗
PubMed2006

Synergistic inhibition of microbial sulfide production by combinations of the metabolic inhibitor nitrite and biocides.

MICs of six broad-spectrum biocides and two specific metabolic inhibitors and fractional inhibitory concentration indexes (FICIs) for controlling a sulfide-producing consortium were determined. Nitrite was synergistic (FICI<1) with all but one biocide due to its specific inhibition of dissimilatory sulfite reductase. Hence, combining nitrite with biocides allows more efficient and cost-effective control of sulfate-reducing bacteria.

Benzalkonium Compounds↗
PubMed1979

Fourteen-year survival of Pseudomonas cepacia in a salts solution preserved with benzalkonium chloride.

A strain of Pseudomonas cepacia that survived for 14 years (1963 to 1977) as a contaminant in an inorganic salt solution which contained commercial 0.05% benzalkonium chloride (CBC) as an antimicrobial preservative, was compared to a recent clinical isolate of P. cepacia. Ammonium acetate was present in the concentrated stock CBC solution, and served as a carbon and nitrogen source for growth when carried over into the salts solution with the CBC. The isolate's resistance to pure benzalkonium chloride was increased step-wise to a concentration of 16%. Plate counts showed 4 x 10(3) colony-forming units per ml in the salts solution. Comparison of growth rates, mouse virulence, antibiotics resistance spectra, and substrate requirements disclosed no differences between the contaminant and a recently isolated clinical strain of P. cepacia. The results indicate that it is critical that pharmaceutical solutions containing benzalkonium chloride as an antimicrobial preservative be formulated without extraneous carbon and nitrogen sources or be preserved with additional antimicrobial agents.

Animals↗
PubMed1980

Inactivation of Mycobacterium bovis in meat products.

The time-temperature combinations necessary to destroy Mycobacterium bovis in meat products were determined. In any given time, M. bovis was destroyed at temperatures 6 to 7 degrees C (ca. 12 degrees F) lower than those necessary for destruction of members of the Mycobacterium avium-Mycobacterium intracellulare complex. Hence, any processing heat adequate to kill M. avium-M. intracellulare-complex organisms will provide a very large safety factor with respect to M. bovis. Benzalkonium chloride treatment of wiener specimens for cultural examination effectively destroyed the normal flora of wiener emulsion without reducing the numbers of M. bovis. Treatment with a phenolic disinfectant followed by formaldehyde vapor was effective in disinfecting equipment contaminated with meat emulsion containing M. bovis.

Animals↗
PubMed1981

Susceptibility of Legionella pneumophila to three cooling tower microbicides.

Investigation of epidemic outbreaks of Legionnaires disease by Center for Disease Control personnel has resulted in the isolation of Legionella pneumophila from water in the air-conditioning cooling towers or evaporative condensers at the site of the outbreak. It is suspected that improperly maintained open, recirculating water systems may play a role in the growth and dissemination of this pathogen. The objective of this study was to determine the antimicrobial activity of three chemically different, commercially available, cooling tower microbicides against L. pneumophila. Using two in vitro test systems, a combination of N-alkyl dimethyl benzyl ammonium chloride and bis (tri-n-butyltin) oxide was found to kill L. pneumophila at a concentration 25 times less than the minimum recommended use concentration, whereas N-alkyl 1,3-propanediamine and methylene bis (thiocyanate) were active at concentrations equal to or greater than the concentrations recommended for use by the manufacturer.

Benzalkonium Compounds↗
PubMed1987

Susceptibility of Torulopsis glabrata in the presence of six antifungal agents determined by comparison of growth at several pHs.

We describe a method using an automated system whereby fungistatic activities can be determined in several conditions. The process was adapted to Torulopsis glabrata, and it showed that benzalkonium chloride, chlorhexidine gluconate, and thimerosal preserve fungistatic activities in acidic medium, whereas acidification reduces the activity of povidone iodine and poloxamer.

Antifungal Agents↗
PubMed1989

Mechanism of resistance to benzalkonium chloride by Pseudomonas aeruginosa.

The mechanisms of resistance of Pseudomonas aeruginosa to benzalkonium chloride (BC) were studied. The effluence of cell components was observed in susceptible P. aeruginosa by electron microscopy, but resistant P. aeruginosa seemed to be undamaged. No marked changes in cell surface potential between Escherichia coli NIHJC-2 and a spheroplast strain were found. The contents of phospholipids (PL) and fatty and neutral lipids (FNL) in the cell walls of resistant P. aeruginosa were higher than those in the cell walls of susceptible P. aeruginosa. The amounts of BC adsorbed to PL and FNL of cell walls of BC-resistant P. aeruginosa were lower than those for BC-susceptible P. aeruginosa. Fifteen species of cellular fatty acids were identified by capillary gas chromatography and gas chromatography-mass spectrometry. The ability of BC to permeate the cell wall was reduced because of the increase in cellular fatty acids. These results suggested that the resistance of P. aeruginosa to BC is mainly a result of increased in the contents of PL and FNL. In resistant P. aeruginosa, the decrease in the amount of BC adsorbed is likely to be the result of increases in the contents of PL and FNL.

Benzalkonium Compounds↗
PubMed2002

Postadaptational resistance to benzalkonium chloride and subsequent physicochemical modifications of Listeria monocytogenes.

Many studies have demonstrated that bacteria, including Listeria monocytogenes, are capable of adapting to disinfectants used in industrial settings after prolonged exposure to sublethal concentrations. However, the consequent alterations of the cell surface due to sanitizer adaptation of this pathogen are not fully understood. Two resistant and four sensitive L. monocytogenes strains from different sources were progressively subcultured with increasing sublethal concentrations of a surfactant, benzalkonium chloride (BC). To evaluate the effects of acquired tolerance to BC, parent and adapted strains were compared by using several morphological and physiological tests. Sensitive strains showed at least a fivefold increase in the MIC, while the MIC doubled for resistant strains after the adaptation period. The hydrophobicities of cells of parent and adapted strains were similar. Serological testing indicated that antigen types 1 and 4 were both present on the cell surface of adapted cells. The data suggest that efflux pumps are the major mechanism of adaptation in sensitive strains and are less important in originally resistant isolates. A different, unknown mechanism was responsible for the original tolerance of resistant isolates. In an originally resistant strain, there was a slight shift in the fatty acid profile after adaptation, whereas sensitive strains had similar profiles. Electron micrographs revealed morphological differences after adaptation. The changes in cell surface antigens, efflux pump utilization, and fatty acid profiles suggest that different mechanisms are used by resistant and sensitive strains for adaptation to BC.

Adaptation, Biological↗
PubMed1969

Comparison of methods for tuberculosis bacteriology.

To improve efficiency of isolation of tubercle bacilli from clinical specimens, the following recommendations are presented. (i) Employ multiple specimens consisting of a combination of morning sputums for the early detection of positives, along with 24-hr sputum pools for the greatest total yield of positives. (ii) When timing is rigorously controlled, Zephiran-trisodium phosphate and sodium hydroxide-acetylcysteine are comparable, but if timing cannot rigidly be controlled, employ the Zephiran-trisodium phosphate digestion procedure to allow the greatest freedom in exposure time with the lowest kill rate to tubercle bacilli. (iii) Employ both an agar medium incubated in 5% CO(2), for the early detection of positives as well as positives in the presence of contaminants, and an egg medium, preferably with CO(2), to increase the yield of positives.

Agar↗