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PubMed1995

Experimental megaileum.

Typical megaileum occurred in young male Wistar rats three months after ileum myenteric plexus denervation. An average of 58.4% denervation of the Auerbach plexus was obtained by serosal application of benzalkonium chloride (0.2% v/v). Denervation was assessed by ganglion cell counts in an 8 nm ring-shaped histological sectfrom the midportion of the treated segment. A morphometric study showed that the increased thickness of the megaileum wall was due to muscle hypertrophy and mucosal hyperplasia. The potential usefulness of this model of megaileum is emphasized.

Animals↗
PubMedDate not supplied

Comparison of the relative toxicity of travoprost 0.004% without benzalkonium chloride and latanoprost 0.005% in an immortalized human cornea epithelial cell culture system.

The purpose of this study was to compare the relative toxicity of a new topical ophthalmic glaucoma medication, travoprost 0.004% without benzalkonium chloride (BAK), with that of commercially available latanoprost 0.005% (preserved with 0.02% BAK) in immortalized human corneal epithelial cells (HCEs). Tissue culture plates (96 well) containing HCEs were divided into 6 groups. Two groups served as negative controls (70% methanol and gentamicin). Another 2 groups--1 in corneal epithelial culture media and the other in a hydroxypropyl (HP)-Guargellable lubricant eyedrop--served as live controls. The travoprost 0.004% without BAK and latanoprost 0.005% groups were exposed to 100 microL of the undiluted solutions. Cells were incubated for 25 min at 37 degree C. A live/dead assay was used to measure the effects of travoprost without BAK and of latanoprost on HCEs compared to 70% methanol and culture medium. Between the 2 glaucoma medications tested, travoprost 0.004% preserved without BAK showed significantly less toxicity on HCEs than did latanoprost 0.005%. This difference may have ramifications in terms of tolerability for patients who use these topical glaucoma drugs on a long-term basis.

Antihypertensive Agents↗
PubMedDate not supplied

Assessment of corneal epithelial integrity after acute exposure to ocular hypotensive agents preserved with and without benzalkonium chloride.

The corneal toxicity of 2 intraocular pressure-lowering agents was compared in a rabbit cornea model with New Zealand White rabbits. Corneal epithelial morphology and cell size were assessed by in vivo confocal microscopy. Baseline microscopic examinations were performed on 1 eye of each animal. Two weeks later, the eyes were bathed for 3 min in travoprost 0.004% preserved without benzalkonium chloride (BAK( or latanoprost 0.005% preserved with 0.02% BAK; the eyes were then rinsed with balanced salt solution, and the corneas were again examined by confocal microscopy (n=4/group). A second group of animals was exposed to the medications through a dosing regimen of 1 drop/min (lpar3 drops total) (n=4/group). In eyes treated with travoprost without BAK (3-min bath), superficial epithelial cells were similar to baseline, as indicated by their visible cell borders and bright nuclei. In contrast, the surface cells in eyes treated with latanoprost were significantly smaller and brighter and had less distinct borders. Surface cell size was significantly smaller as compared with baseline size and as compared with rabbits treated with travoprost without BAK for 3 min. Similar effects on corneal epithelial cell morphology were observed with the 1-drop/min dosing regimen. In this rabbit model, travoprost 0.004% preserved without BAK did not cause corneal epithelial toxicity; latanoprost 0.005% induced superficial cell loss, most likely caused by the presence of a relatively high concentration of BAK (0.02%).

Administration, Topical↗
PubMedDate not supplied

Spermicidal activity of a new contraceptive sponge.

An open, crossover study evaluated the spermicidal efficacy and irritative potential of the Protectaid sponge. Postcoital tests were conducted in nine healthy couples under control conditions (no sponge) and with the sponge. Microscopic examination of postcoital mucus from the female partners showed that sperm entered the cervix in all nine controls, whereas entry was completely prevented by the sponge in four of nine women. None of the participants showed colposcopic evidence of mucosal irritation while using the sponge. Colposcopic abnormalities were evident in two of nine women during control testing. The urgent need for female-controlled contraceptive methods with the potential to protect against sexually transmitted diseases makes this low-dose spermicidal vaginal sponge an effective and safe alternative.

Adolescent↗
PubMedDate not supplied

Effects of common ophthalmic preservatives on ocular health.

Preservatives are an important component of ophthalmic preparations, providing antimicrobial activity in the bottle and preventing decomposition of active drug. Often underrecognized, however, are the significant cytotoxic effects of preservatives associated with long-term therapy and especially use of multiple preserved drugs. The most common preservatives in ophthalmic preparations for glaucoma and surface eye disease-benzalkonium chloride (BAK), chlorobutanol, sodium perborate, and stabilized oxychloro complex (SOC)-were reviewed. Compared with other preservatives, SOC caused the least amount of damage to rabbit corneal epithelial cells. BAK has demonstrated cytotoxic effects in cell culture, as well as in animal and human studies. Physicians should consider treatment with new-generation preparations containing low-risk preservatives such as SOC, especially in patients receiving multiple ophthalmic medications.

Animals↗
PubMed2004

Effect of biocides on S. cerevisiae: relationship between short-term membrane affliction and long-term cell killing.

The long-term action of recommended (RC) and near-recommended concentrations of several commercial biocides (Lonzabac 12.100, Genamin CS302D, benzalkonium chloride and 2-phenoxyethanol) on cells of S. cerevisiae wild-type strain DTXII was described using plating tests while short-term effects were determined using the potentiometric fluorescent probe diS-C3(3) that detects both changes in membrane potential and impairment of membrane integrity. A 2-d plating of cells exposed to 0.5xRC of benzalkonium chloride and Genamin CS302D for 15 min showed a complete long-term cell killing, with 2-phenoxyethanol the killing was complete only at 2xRC and Lonzabac caused complete killing at RC but not at 0.5xRC. The diS-C3(3) fluorescence assay performed immediately after a 10-min biocide exposure revealed several concentration-dependent modes of action: Lonzabac at 0.5xRC caused a mere depolarization, higher concentrations causing gradually increasing cell damage; benzalkonium chloride and Genamin CS302D rapidly damaged the membrane of some cells and depolarized the rest whereas 2-phenoxyethanol, which had the lowest effect in the plating test, produced a concentration-dependent fraction of cells with impaired membranes. Cell staining slightly increased during the diS-C3(3) assay; addition of a protonophore showed that part of the remaining undamaged cells retained their membrane potential. Comparison of short-term and long-term data implies that membrane depolarization alone is not sufficient for complete long-term killing of yeast cells under the action of a biocide unless it is accompanied by perceptible impairment of membrane integrity. The results show that the diS-C3(3) fluorescence assay, which reflects the short-term effects of a biocide on cell membranes, can be successfully used to assess the microbicidal efficiency of biocides.

Anti-Infective Agents↗
PubMed2003

[Tolerance and effectiveness of oxymetazoline and xylometazoline in treatment of acute rhinitis].

BACKGROUND: Local alpha-sympathomimetics in hydrous solution are well known in the therapy of acute rhinitis and sinusitis. However, added preservatives like benzalkonium chloride have a negative effect on compatibility. PATIENTS AND METHOD: A total of 307 patients with acute rhinitis entered the study. The treatment with oxymetazoline with preservative, oxymetazoline without preservative and xylometazoline with preservative was evaluated. RESULTS: This randomised, double-blind, multi-centered, verum-controlled tolerance study confirmed that the local sympathomimetics oxymetazoline and xylometazoline are well tolerated in the treatment of acute rhinitis. When evaluated according to the parameters "feeling of dryness in nasal mucosa" and "burning sensation", the Nasivin sanft 0.05% spray, which contains the active agent oxymetazoline without preservatives, proved to be considerably superior to preparations containing the preservative benzalkonium chloride. CONCLUSION: Preparations without preservatives should be the preferred choice of treatment for acute rhinitis.

Acute Disease↗
PubMed1998

[Effect of topical corticosteroids and topical antihistaminics on ciliary epithelium of human nasal mucosa in vitro].

A normal ciliary beat frequency of ciliated cells is necessary for the mucociliary clearance of the nose and paranasal sinuses. An in vitro investigation was performed to evaluate the influence of topical corticosteroids and antihistamines on the ciliary beat frequency of human nasal mucosa. The nasal sprays examined contained the corticosteroids budesonide or fluticasone propionate and the topical antihistamines azelastine or levocabastine. All tests were performed on cell cultures of human nasal mucosa during constant conditions. Three of the four nasal sprays tested contained benzalkonium chloride as preservative. An irreversible cessation of ciliary movement was observed in all cells exposed to nasal sprays containing benzalkonium chloride in a 50 per cent solution. The nasal spray containing budesonide was benzalkonium chloride-free and caused minor but fully reversible decreases in ciliary beat frequency after 20 min. As benzalkonium chloride can cause complete standstill of ciliary beat frequency in vitro in human nasal mucosa, we recommend that this preservative should not be used anymore in topical nasal medications.

Administration, Topical↗
PubMed2000

Association of TNFA gene polymorphism at position -308 with susceptibility to irritant contact dermatitis.

Mechanisms underlying susceptibility to skin irritants are not clearly understood. Cytokines play a key role in inflammation, and functional polymorphisms in cytokine genes may affect responses to irritants. We investigated the relationship between polymorphism in the tumor necrosis factor (TNF) alpha-chain gene and responses to irritants. Volunteers (n=221) tested with sodium dodecyl sulfate (SDS) and benzalkonium chloride (BKC) were divided into responders and nonresponders and high and low irritant-threshold groups. DNA was assayed for the TNF-308 polymorphism by a polymerase chain reaction-restriction fragment length polymorphism method. There was a significant increase in the A allele (P=0.030) and AA genotype (P=0.023) in both the SDS low irritant-threshold group and in SDS responders (A allele P=0.022, AA genotype P=0.048). In the BKC low irritant-threshold group, we found a significant increase in the A allele (P=0.002) and AA genotype (P=0.016). Individuals with a low threshold to both irritants demonstrated a significant increase (P=0.002) in the A allele. This is the first description of a nonatopic genetic marker for irritant susceptibility in normal individuals. Genotyping for the TNF-308 polymorphism may thus contribute to screening of individuals deemed at risk of developing irritant contact dermatitis.

Adolescent↗
PubMed2000

Corrosive injuries of the esophagus in newborns.

To evaluate the morbidity and mortality of corrosive esophageal injuries (CEI) in the neonatal period, the records of 184 children hospitalized following caustic ingestion over a 10-year period from January 1987 to November 1997 were reviewed. Eight (4.3%) were newborns (5 boys and 3 girls). The mean age of the newborns was 12 days (range 1-28). The ingested caustic materials were benzalkonium chloride in six patients and trichloroacetic acid in two. Oropharyngeal examination and esophagoscopy were performed for diagnosis. Hyperemia and fibrin plaques were present in the oropharynx in all patients. The management consisted of endotracheal intubation, antibiotics, corticosteroids, and total parenteral nutrition. Pneumonia and sepsis developed in three patients and one died of sepsis. Stenosis developed in two patients, who were treated three times with antegrade dilatations. The morbidity was 62.5% (five patients) and the mortality was 12.5% (one) in newborns with CEI. These results indicate that ingestion of a caustic substance results in high morbidity and mortality in newborns. Parents and nurses should be warned about this risk.

Benzalkonium Compounds↗
PubMed2002

Selective chemical ablation of the enteric plexus in mice.

Although genetically aganglionic mice such as piebald lethal and lethal spotted mice exhibit striking similarities to the human condition of Hirschsprung's disease (HD), the aganglionic segment is very short and always located in the distal part of the rectum. Topical application of benzalkonium chloride (BAC) to the rectum of rats has been reported to result in segmental aganglionosis. To induce chemical ablation of the enteric plexus in mice to produce an aperistaltic narrow segment simulating HD, 32 mice were divided into three groups: (1) abdominal (n=12), for sigmoid colon treatment; (2) rectal (n=10), for rectum treatment; and (3) controls (n=10). For groups 1 and 2, 0.1% BAC was applied to a 1-cm serosal surface of the bowel for 15 min. In the controls, isotonic saline was applied in this fashion. A detailed histologic examination was performed using hematoxylin and eosin staining and acetylcholinesterase histochemistry. Ten animals (9 in group 1 and 1 in group 2) died 1 to 9 weeks after BAC treatment. Autopsy revealed a narrow segment of bowel at the site of BAC treatment and marked dilatation of the bowel proximal to the narrow segment. The remaining animals were killed 12 weeks after BAC treatment. Histologic examination demonstrated normal myenteric and submucous plexuses in the controls, whereas there was a total lack of innervation in the BAC-treated segments.Topical application of BAC thus successfully produced a narrow aganglionic segment of bowel in normal mice. This model provides the basis for future studies to investigate the pathophysiology of HD and megacolon and for comparison with genetically aganglionic mice.

Animals↗
PubMed2004

A simple reconstructed human epidermis: preparation of the culture model and utilization in in vitro studies.

The preparation of a reconstructed human epidermis is described with examples of its utilization in in vitro studies. The model was obtained by culturing normal human keratinocytes at high cell density for 14 days in serum-free and high calcium (1.5 m M) medium on an inert polycarbonate filter at the air-liquid interface. These stratified cultures showed histological features similar to those observed in vivo in the epidermis: a proliferating basal layer and differentiating spinous, granular, and cornified layers. Electron microscopy illustrated lamellar bodies, junctions and keratohyalin granules. Immunofluorescent localization of epidermal markers (keratins 14 and 10, involucrin and filaggrin) revealed typical differentiation. This in vitro reconstructed tissue was used in studies of toxic effects of chemicals. The modelled tissue showed progressive cytotoxicity of a skin irritant (benzalkonium chloride) and a sensitizer (dinitrochlorobenzene) as assessed by MTT assay. Moreover, differential release of interleukin-1alpha and interleukin-8 were measured after 20 h of incubation allowing the irritant to be distinguished from the sensitizer. Permeation studies indicated efficient barrier function of the reconstructed epidermis, as well as metabolizing properties towards hormones. This model can be custom-made and is potentially useful for studies involving keratinocytes in the epidermis, in basic science, dermatology or toxicology.

Benzalkonium Compounds↗
PubMed2002

The effect of benzalkonium chloride on rabbit nasal mucosa in vivo: an electron microscopy study.

In this study we investigated the histopathological changes of nasal mucosa after the use of topical benzalkonium-chloride solution. In the study, 28 male New Zealand white rabbits were used. The animals were divided into two groups. In the first group, 50 micro l of 0.001% benzalkonium-chloride solution was sprayed into the right nostril and 50 micro l of 0.9% saline into the left twice daily for 14 days. In the second group, the same solutions were applied twice daily for 28 days. All of the biopsies from each nasal cavity were processed for electron microscopy. In the nostrils treated with 0.001% benzalkonium chloride, there were areas with obvious squamous cell metaplasia. Some cells showed broken cristae of the mitochondria. Degenerative changes in the supportive and olfactory cells, deformation of nuclei and the increase of heterochromatin were observed. The present investigation has shown that the application of topical benzalkonium chloride does induce degenerative morphologic changes in the nasal mucosa in rabbits in vivo.

Administration, Topical↗