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A case of fatal benzalkonium chloride poisoning.

Five elderly persons with senile dementia accidentally ingested Hoesmin, a 10% aqueous solution of benzalkonium chloride (BAC). The condition of one patient, an 84-year-old woman whose lips and oral cavity became erythematous, gradually deteriorated. Although gastric lavage was performed, the patient died 3 h after ingestion of Hoesmin. Autopsy revealed corrosive changes of the mucosal surfaces of the tongue, pharynx, larynx, esophagus and stomach which may have come in contact with BAC. In addition, BAC was detected in the serum. We conclude that the patient died of BAC poisoning. Fatal BAC poisoning is rare and autopsy findings in only a few cases of BAC poisoning have been reported. Our findings emphasize the risk of oral ingestion of BAC.

Aged↗

Ocular surface changes induced by topical application of latanoprost and timolol: a short-term study in glaucomatous patients with and without allergic conjunctivitis.

BACKGROUND: This study evaluated the conjunctival effects of latanoprost and timolol, both of which contain benzalkonium chloride, in patients with primary open-angle glaucoma (POAG), with and without a history of allergic conjunctivitis (AC). METHODS: Two groups of 25 patients with and without a positive history for AC were studied. After a 21-day wash-out period patients were randomized to 14 days treatment with latanoprost or with timolol, in a cross-over fashion. The following parameters were evaluated on days 0 and 14: number of white blood cells, ferning test, conjunctival impression cytology, subjective symptoms, and objective ocular changes. RESULTS: Latanoprost caused: (a) an increase in eosinophils in both groups and reduction in lymphocytes only in the group with a history of AC; (b) alterations in ferning test and impression cytology only in AC patients; and (c) development of subjective symptoms and objective signs only in non-AC glaucomatous subjects. Timolol therapy was responsible only for the occurrence of subjective symptoms and objective signs in non-AC patients. CONCLUSION: Latanoprost treatment induces ocular surface changes which are more evident in POAG patients who are also affected by AC. These findings are probably related to the very high latanoprost concentration of benzalkonium chloride and to its bedtime administration, which further amplifies the toxicity.

Administration, Topical↗

Megaesophagus in rats.

The objective of this study was to determine whether myenteric denervation of the abdominal esophagus using benzalkonium chloride (BAC) leads to esophageal achalasia with changes of the muscle propria and epithelial cell proliferation. The treatment led to megaesophagus 3 months after BAC application. Denervation of the esophagus induced muscle hypertrophy and increased epithelial cell proliferation. The imbalance of the neurotransmitters may play a role in these morphokinetic changes.

Animals↗

The relationship between myenteric neuronal denervation, smooth muscle thickening and epithelial cell proliferation in the rat colon.

The effects of myenteric neuronal denervation on smooth muscle thickening and epithelial cell proliferation were studied in the descending colon of rats treated by serosal application of 2 mM benzalkonium chloride (BAC) for 30 min. Control animals were treated with saline (0.9% NaCl). The animals were divided into six groups of 13 animals each and killed 10, 45 and 120 days after BAC treatment. A significant reduction in neuron number was observed in the myenteric plexus of animals treated with BAC, as well as smooth muscle thickening and an increase in crypt cell population, crypt cell production per crypt and a decrease in cell cycle time. These findings permit us to conclude that a relationship may exist between the increase of epithelial cell proliferation, smooth muscle thickening and myenteric neuron denervation in the descending colon caused by BAC, the latter probably playing an important role in the integration of the other two.

Animals↗

Plasticity of interstitial cells of Cajal: a study of mouse colon.

Ablation of the myenteric plexus in mouse colon with the detergent benzalkonium chloride (BAC) is followed by considerable recovery of the nerves, indicating that this plexus is capable of regeneration and has plasticity. Interstitial cells of Cajal (ICC) are closely associated with enteric nerves, and the acquisition and maintenance of their adult phenotype are nerve-dependent. Little is known about the regenerative processes of ICC or about the possible dependence of these processes on neurons. To address these questions, we ablated the myenteric plexus in the mouse colon with BAC and followed changes in the adjacent ICC (ICC-MP) from day 2 to day 70 after treatment, by using c-kit-immunohistochemistry and electron microscopy. In the untreated area, c-kit-positive cells and ICC-MP with normal ultrastructural features were always present. The region partially affected by BAC contained some c-kit-positive cells, and either normal or vacuolated ICC-MP were observed by electron microscopy. Moreover, at days 60-70, ICC-MP with particularly extended rough endoplasmic reticulum were present in this area. In the treated area, either denervated or reinnervated, c-kit-positive cells were always absent. By day 14 after BAC treatment, nerve fibers had started to grow back into the treated region and, in the reinnervated area, cells with fibroblast-like features appeared and were seen to contact both nerve endings and smooth muscle cells and to acquire some typical ICC features. Thus, ICC are vulnerable to external insult but appear to have some ability to regenerate.

Animals↗

Multiple mechanisms contribute to myenteric plexus ablation induced by benzalkonium chloride in the guinea-pig ileum.

Ablation of rat myenteric plexus with benzalkonium chloride has provided a model of intestinal aganglionosis, but the degenerative responses are not well understood. We examined the effects of this detergent on neurons and glia, including expression of c-Myc, c-Jun, JunB, and c-Fos, and on immunocytes in the guinea-pig ileum. Benzalkonium chloride (0.1%) or saline was applied to the serosal surface of distal ileum. Tissues were analyzed 2, 3, or 7 days later and compared with cyclosporine-treated and untreated animals. More than 90% of myenteric neurons were destroyed in ileal segments 3-7 days after benzalkonium-chloride treatment. Glia withdrew processes from around neurons after 2 days and were mostly gone after 3 days. Neuronal c-Myc began to disappear while c-Fos, c-Jun, and JunB were evident in some neuronal nuclei after 2 or 3 days. After 3 days, widespread apoptosis was evident in the myenteric plexus. Populations of T cells, B cells, and macrophage-like cells in untreated and saline-treated myenteric plexuses were substantially increased 3 and 7 days after benzalkonium-chloride treatment. Cyclosporine delayed significant neuronal loss. We conclude that a variety of degenerative mechanisms may be active in this model, including an immune response which may actively contribute to tissue destruction.

Animals↗

Evaluation of benzalkonium chloride chemoneurolytic proximal gastric vagotomy.

BACKGROUND: Transmucosal chemoneurolytic injection of benzalkonium chloride (BAC) has previously been shown to duplicate operative proximal gastric vagotomy (PGV) in controlling gastric acid secretion. In this study, BAC was evaluated as to efficacious dose, methods of delivery, and systemic toxicities. METHODS: Sham celiotomy, operative PGV controls, transmucosal injections through a gastrotomy, and transserosal injections of BAC (saline controls, 0. 625, 1.25, 2.5, 5.0, 10 mg BAC/kg body wt) were administered to Sprague-Dawley rats. After 3 months the rats underwent Congo red testing (CRT), horseradish peroxidase (HRP) neuronal staining, and necropsy. The color density change of the gastric mucosa from basic to acidic demonstrated by the CRT at the time of necropsy was used to calculate the residual anatomic acid-secreting area. Prior to necropsy, subserosal HRP injections into the anterior and posterior stomach walls assayed vagal neuronal viability via retrograde axonal flow. Results were compared by an ANOVA. RESULTS: The results demonstrated that 1.25-10 mg/kg transmucosal BAC replicated the results of operative PGV; 2.5 mg/kg was found to be the most effective dose. All injection groups including saline controls demonstrated similar diminished vagal retrograde axonal flow by HRP testing consistent with local BAC chemoneurolytic effects. No systemic toxic symptoms were observed after tail vein intravenous BAC 1.25, 2.5, and 5.0 mg/kg. CONCLUSIONS: These efficacy studies have demonstrated BAC's potential utility in the performance of endoscopic transmucosal chemoneurolytic PGV.

Animals↗

Functional coupling of GABA(B) receptors with G proteins that are sensitive to N-ethylmaleimide treatment, suramin, and benzalkonium chloride in rat cerebral cortical membranes.

Although it is known that GABA(B) receptors are negatively coupled to adenylyl cyclase, the detailed selectivity of functional interaction between GABA(B) receptors and Gi subfamily members is still ambiguous. (+/-)-Baclofen-stimulated high-affinity GTPase activity, which was competitively antagonized by 2-hydroxy-saclofen, was attenuated by pretreatment of the membranes with N-ethylmaleimide (NEM) in a concentration- and incubation period-dependent manner. The NEM-pretreated (50 microM, 15 min at 4 degrees C) membranes restored the (+/-)-baclofen-sensitive high-affinity GTPase activity when reconstituted with pertussis toxin-sensitive bovine brain G proteins. Among recombinant rat Galpha subunits, G(i alpha(-2)) appeared most effective as compared with other subunits (G(i alpha(-2)) > G(i alpha(-3) > G(i alpha(-1) = G(o alpha). The GABA(B) receptor-mediated high-affinity GTPase activity was also completely eliminated by 100 microM suramin and by 100 microM benzalkonium chloride. These results indicate that GABA(B) receptors in rat cerebral cortex couple to NEM-sensitive G proteins, in particular Gi2, which are sensitive to suramin and benzalkonium chloride.

Adenylate Cyclase Toxin↗

Myenteric denervation differentially reduces enteroendocrine serotonin cell population in rats during postnatal development.

The enteric nervous and enteroendocrine systems regulate different processes in the small intestine. Ablation of myenteric plexus with benzalkonium chloride (BAC) stimulates epithelial cell proliferation, whereas endocrine serotonin cells may inhibit the process. To evaluate the connection between the systems and the influence of myenteric plexus on serotoninergic cells in rats during postnatal development, the ileal plexus was partially removed with BAC. Rats were treated at 13 or 21 days and sacrificed after 15 days. The cell bodies of myenteric neurons were stained by beta NADH-diaphorase to detect the extension of denervation. The number of enteroendocrine cells in the ileum was estimated in crypts and villi in paraffin sections immunostained for serotonin. The number of neurons was reduced by 27.6 and 45% in rats treated on the 13th and 21st days, respectively. We tried to establish a correlation of denervation and the serotonin population according to the age of treatment. We observed a reduction of immunolabelled cells in the crypts of rats treated at 13 days, whereas this effect was seen in the villi of rats denervated at 21 days. These results suggest that the enteric nervous system might control the enteroendocrine cell population and this complex mechanism could be correlated to changes in cell proliferation.

Animals↗

Evaluation of fungicidal efficacy of benzalkonium chloride (Steramina G u.v.) and Virkon-S against Microsporum canis for environmental disinfection.

The aim of this study is to evaluate the antifungal efficacy of Steramina G u.v. (10% solution of alkyldimetylbenzylammonium chloride; Formenti Grünenthal) and Virkon-S (multipurpose system; Antec International) against Microsporum canis-infected hairs and spores. Samples were collected from a random sample of household cats and from subjects from catteries. Seventy M. canis-positive hairbrushes containing furs, keratin scales and other organic material were treated with each of the two disinfectants, using concentrations recommended by the manufacturer's instructions (2% and 1% for Steramina G u.v. and Virkon-S, respectively). Each brush remained in contact with the antifungal solution for 10 min. After this period, the brushes were air-dried, then seeded into mycobiotic agar, and incubated for up to 21 days at 28 degrees C. The disinfectants were considered effective if dermatophytes failed to grow. Steramina G u.v. was effective in 97.14% of samples and Virkon-S in 87.14%. The antifungal activity of Steramina G u.v. against M. canis was significantly higher (p < 0.05) than that of Virkon-S.

Animals↗

A comparison of methods for collecting clean-catch urine specimens in a clinic population of obstetric patients.

A descriptive study comparing the use of the gram-positive skin cleansers Zephiran and hexachlorophene to Prepodyne, a gram-negative cleanser, was performed upon 1, 469 specimens from patients attending the prenatal clinic of a large university hospital. The period prevalence rate of symptomatic and asymptomatic bacteriuria in 1, 350 patients was 11.5 per cent. Group teaching compared to individualized teaching of the patients to collect their own aliquots did not appear to have a measurable effect upon the levels of bacteriuria. Significant differences were found at p equals 0.05 between all the serially sampled groups using the different cleansers. No significant difference was found between the two groups using only hexachlorophene when compared for differences between patient-collected and nurse-collected specimens; nevertheless, the patient-collected specimens had greater proportions of low bacterial counts than those collected by the nurses. This study indicates that carefully instructed patients in large clinic populations are more efficient than the nurses when they collect their own midstream specimens, using an adequate cleansing agent. An analysis of the rates disclosed that Zephiran cleansing had high contamination levels, whereas Prepodyne significantly reduced contamination of the specimens. However, the possible reduction of the rate of 10-5 specimens to 9.1 per cent in the group using Prepodyne did not rule out the possibility of reduced specificity, and the hazard of false-negative results occuring with the use of gram-negative skin cleansers requires further study.

Age Factors↗

Benzalkonium chloride toxicity to the human cornea.

A 36-year-old woman fitted with a soft contact lens after an uneventful extracapsular cataract extraction was wearing her aphakic lens successfully until she switched her lens-soaking solution to an isotonic solution of boric acid, potassium chloride, and sodium carbonate preserved with benzalkonium chloride and edetic acid. After three days her eye became inflamed and vision decreased. No endothelial damage was apparent and the anterior chamber showed 2+ cell and flare reaction. Three weeks after removal of the lens and fitting with an aphakic lens visual acuity was 6/9 (20/30). Study of the preservative by a semiquantitative dilution method together with the clinical evidence in this case proved the cytotoxic effect of benzolkonium chloride when used to sterilize soft contact lenses.

Adult↗

Toxic endothelial degeneration in ocular surface disease treated with topical medications containing benzalkonium chloride.

We examined a 56-year-old man with keratoconjunctivitis sicca and marked ocular surface disease in whom the prolonged frequent use of topical medications containing the preservative benzalkonium chloride was associated with corneal endothelial damage requiring corneal transplantation in one eye. The histopathologic findings on examination of the excised button were consistent with toxic endothelial disease. Postoperatively, the patient's symptoms continued until the preservative-containing medications were substituted with nonpreserved saline eyedrops.

Benzalkonium Compounds↗