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Ototoxic effect of iodine disinfectants.

It had been suggested that disinfectants which could trickle into the middle ear through a perforated drum during the skin sterilization preceding otosurgery might cause inner ear damage resulting in deafness. In animal experiments it has been shown that chlorhexidine, benzethonium- and benzalkonium chloride, when introduced into the tympanic cavity of guinea pigs, will cause rather extensive damage to the neuroepithelial receptors of the inner ear. In the present study, iodine, frequently used for skin disinfection, has been investigated as regards ototoxicity by locally exposing the middle ear in guinea pigs. The duration of exposure was 10, 30, or 60 min. The animals were sacrificed 2 weeks later and the organs of Corti and neuroepithelial receptors of the vestibular part of the inner ear were studied as surface preparations in phase-contrast microscopy. It was found that slight damage had occurred in the basal parts of the organ of Corti of those ears exposed to iodine or iodophor in 70% alcohol for 60 or 30 min and damage to the vestibular receptors was observed in ears exposed to iodophor in 70% alcohol for 60 min. In ears exposed to iodine or iodophor in aqua dest., no damage to the inner ear sensory epithelia was revealed.

Animals↗

Ototoxic effect of quaternary ammonium compounds.

In earlier investigations by the author it has been shown that chlorhexidine, when introduced into the middle ear of guinea pigs, caused serious damage to the inner ear. The present investigation was performed in order to study if the quaternary ammonium compounds benzethonium chloride and benzalkonium chloride, frequently used for skin disinfection, can also induce inner ear damage when introduced into the tympanic cavity of guinea pigs. The disinfectants in question, at a concentration of 0.1% and in a solution of aqua dest. or 70% alcohol, were introduced into the animals' middle ear for exposure times of 10, 30, or 60 min. The animals were sacrificed 2 or 9 weeks after the exposure and the organ of Corti and vestibular neuroepithelia were studied as surface preparations with phase contrast microscopy. It was found that most of the ears exposed to the disinfectants had suffered damage, affecting both the vestibular and cochlear parts of the inner ear. The extent of the damage was related both to the duration of exposure and to the length of the animals' survival after the exposure. Furthermore it was found that the tympanic cavity and the perilymphatic spaces of vestibulum and cochlea were pathologically changed.

Acoustic Maculae↗

Contact allergy to various components of topical preparations for treatment of external otitis.

Patients suffering from chronic external otitis had developed contact allergies to one or more compounds of topical preparations in 40% of 142 tested patients. Neomycin and framycetin caused most of the allergic reactions (16.2%) followed by chinoform (7.0%), chloramphenicol and polymyxin (4.2%). Preservatives of the topical otic preparations such as benzethonium chloride (8.5%), benzalkonium chloride (6.3%) and thimerosal (merthiolate) (5.6%) were also common causes of allergic reactions. An epicutaneous test (patch test) using compounds in topical preparations should be done in cases of prolonged, treatment resistant external otitis.

Anti-Infective Agents, Local↗

Aspects of the antimicrobial efficacy of grapefruit seed extract and its relation to preservative substances contained.

The antimicrobial efficacy as well as the content of preservative agents of six commercially available grapefruit seed extracts were examined. Five of the six extracts showed a high growth inhibiting activity against the test germs Bacillus subtilis SBUG 14, Micrococcus flavus SBUG 16, Staphylococcus aureus SBUG 11, Serratia marcescens SBUG 9, Escherichia coli SBUG 17, Proteus mirabilis SBUG 47, and Candida maltosa SBUG 700. In all of the antimicrobial active grapefruit seed extracts, the preservative benzethonium chloride was detected by thin layer chromatography. Additionally, three extracts contained the preserving substances triclosan and methyl parabene. In only one of the grapefruit seed extracts tested no preservative agent was found. However, with this extract as well as with several self-made extracts from seed and juiceless pulp of grapefruits (Citrus paradisi) no antimicrobial activity could be detected (standard serial broth dilution assay, agar diffusion test). Thus, it is concluded that the potent as well as nearly universal antimicrobial activity being attributed to grapefruit seed extract is merely due to the synthetic preservative agents contained within. Natural products with antimicrobial activity do not appear to be present.

Anti-Bacterial Agents↗

Total protein determination in urine: elimination of a differential response between the coomassie blue and pyrogallol red protein dye-binding assays.

BACKGROUND: The total protein content of urine is a good index of renal function, but its determination is unreliable. Protein dye-binding assays are simple, but they characteristically lack a uniform response to different proteins. METHODS: We investigated a differential response of the Sigma Microprotein Coomassie Brilliant Blue (CBB) and Pyrogallol Red-molybdate (PRM) protein dye-binding assays to urine, using human albumin, albumin/globulin, or urinary protein as calibrator. RESULTS: The urine protein values (n = 60) obtained with the CBB assay were 110-13 500 mg/L (mean, 2390 mg/L) compared with 160-18 300 mg/L (mean, 3470 mg/L) obtained with the PRM assay (CBB:PRM protein concentration ratio, 0.46-0.88, mean, 0. 69 +/- 0.10). The differential response was highly reproducible as indicated by Sigma urine control Level 1 (within-day CBB:PRM ratio, 0.68 +/- 0.02; between-day CBB:PRM ratio, 0.67 +/- 0.04) and Sigma urine control Level 2 (within-day CBB:PRM ratio, 0.60 +/- 0.01; between-day CBB:PRM ratio, 0.59 +/- 0.02). The use of urinary protein as a calibrator (rather than human albumin) greatly improved the agreement between the assays when applied to urine (y(CBB) = 0. 972x(PRM) - 16 vs y(CBB) = 0.685x(PRM) + 17). In studies using urine controls, this calibrator also improved agreement between the CBB, PRM, trichloroacetic acid (TCA), and benzethonium chloride protein methods and, to a lesser extent, agreement with the TCA-Ponceau S method. CONCLUSION: The use of a urinary protein calibrator improves the agreement between different methods used to determine total protein in urine.

Albumins↗

Occupational allergic contact dermatitis from alkylammonium amidobenzoate.

Quaternary ammonium compounds are water-soluble antimicrobials which are widely used in disinfectants, sterilizers, skin cleansers and antiseptic creams. One quaternary ammonium compound, alkylammonium amidobenzoate (Osmaron B) has for decades been used in udder ointments. Here we present a ship technician with occupationally induced sensitization to alkylammonium amidobenzoate. The diagnosis was reached only when it emerged, after careful questioning, that the patient was exposed to a substance peculiar to his workplace but not to his occupation and was then patch tested for it. It turned out that an udder ointment had been used at the patient's workplace as a hand ointment. Patch testing was positive to the patient's hand ointment, and Osmaron B at 0.1-0.01% in petrolatum. Other sensitizing quaternary ammonium compounds, namely benzalkonium chloride, benzethonium chloride, benzoxonium chloride, N-benzyl-N,N-dihydroxyethyl-N-cocosalkyl-ammonium chloride, cetalkonium chloride, cetylpyridinium chloride, cetrimonium bromide, chloroallylhexaminium chloride, dequalinium chloride, domiphen bromide, methylbenzethonium chloride and 2,3-epoxypropyl trimethyl ammonium chloride are reviewed briefly. The importance of patch testing to all materials in use by the patient is emphasized. It is also important to select non-allergenic hand creams for use at work places.

Benzoates↗

Cetylpyridinium tetrachlorozincate as standard for tenside titration. Analytical methods with 1,3-dibromo-5,5-dimethylhydantoin (DBH) in respect to environmental and economical concern, part 19.

The determination of the cationic active disinfectants benzalkonium chloride, benzethonium chloride, cetrimide, and cetylpyridinium chloride according to PH. EUR. 2002 resp. supplement 4.3/2003 can be improved using the DBH-method. By application of column extraction the iodide determination can be performed in the organic layer by visual indication. However, titration in aqueous solution with sodium dodecyl sulphate as titrant and methyl orange resp. bromophenol blue as indicator can be performed more simple. Cetylpyridinium tetrachlorozincate is recommended as a standard for tenside titration.

Azo Compounds↗

[Study on separation of epirubicin and doxorubicin isomers by displacement chromatography].

Displacement chromatography was successfully used to separate, at the preparative scale, a binary isomer mixture of epirubicin and doxorubicin, which are anthracycline antitumor antibiotics, on an analytical column (Kromasil KR100-10C18 column, 250 mm x 4.6 mm i.d., 10 microm). Displacement parameters such as the type and the concentration of displacer, the composition and the flow-rate of mobile phase were investigated. The displacer employed was 30 g/L benzethonium chloride. The flow-rate was 0.2 mL/min. Loading of feed at lower initial organic level of mobile phase coupled with displacement at higher organic level was found to give efficient separation. The binary isomer mixture of 30 mg was separated on the analytical column. The results have indicated that displacement mode had high efficiency, greatly reduced solvent consumption in the process of purification, and offered the possibility of both high resolution and high loading. It has also demonstrated again that high performance displacement chromatography is one of the effective methods for the purification of therapeutic compounds in industrial processes.

Antibiotics, Antineoplastic↗

[Ovicidal effects of heat and disinfectants on Syphacia muris estimated by in vitro hatching].

The ovicidal effects of heat and various chemical disinfectants on an oxyurid rat nematode Syphacia muris were investigated, using the hatching methods in artificial intestinal juice. The eggs were collected from the perianal skin of spontaneously infected rats by means of a piece of transparent adhesive tapes, and these eggs were treated with each disinfectant for two hours. It was found that 70% ethanol and 80 degrees C 30 min treatments killed almost all of the eggs. However, a small number of the eggs tested was killed by 0.02% chlorhexidine digluconate or 0.05% benzethonium chloride. Alcide, 3% saponated cresol solution, 50% isopropanol, 10 ppm sodium hypochlorite and 5 ppm iodophol had some effects against the eggs, but they didn't kill the eggs completely. A biological assay through infection of the eggs to rats might be necessary because the effects of 2% formalin on the eggs were not determined by the hatching methods.

Animals↗

Hydrofluoric acid burns.

Hydrofluoric acid is used in a variety of industries and poses a considerable medical hazard. The dual mechanism of injury makes hydrofluoric acid burns among the most severe and lethal seen. Prompt treatment with copious irrigation, iced benzethonium or benzalkonium soaks, calcium gluconate gel application and calcium gluconate injections may well prove to be lifesaving.

Accidents, Occupational↗

Basic studies on the viability of El Tor vibrios.

Quantitative data are presented on the viability of El Tor vibrios in various foodstuffs under different conditions. El Tor vibrios were found to have a very short life in water at -20 degrees C, but in various nutrient media, such as skim milk, sugar solution or meat extract, they could live for more than a month at this temperature; the survival rate was always much higher when the vibrio suspension was cooled rapidly to -72 degrees C and stored at this temperature.The optimum pH for the growth and survival of El Tor vibrios is 6-8, and the optimum osmotic pressure 250 mOsm-700 mOsm. The resistance of El Tor vibrios to disinfectants is lower than that of salmonellae and Escherichia coli. The El Tor vibrios are more resistant than classical cholera vibrios to such disinfectants as benzethonium chloride and o-dichlorobenzene. They are not resistant to sodium hypochlorite or bleaching powder at 6 ppm.The results of the investigation emphasize the necessity of immediate and proper disinfection of foodstuffs contaminated with El Tor vibrios, and indicate the possibility of survival of the organisms for long periods under favourable conditions.

Bacteriological Techniques↗

Quantitative analysis of preservatives drug preparations by microbiological assay.

The stability of a preservative selected for incorporation into a drug preparation can only be determined by suitable tests applied at regular intervals, preferably over long periods. Chemical tests are available for a number of preservatives and some of them appear to be adequate but difficulties have occurred from time to time and studies were undertaken to develop microbiological tests. Chemical methods are usually more precise than biological assays but do not always measure the antimicrobial activity of the preservative as accurately. It is always possible that a preservative may break down, losing some of its effectiveness even though the chemical determinant upon which the test is based remains intact.Two assay methods were studied. One, a plate-diffusion procedure, was found suitable for assaying formol and preservatives containing mercury. Preservatives such as phenol, benzethonium chloride and others do not diffuse in an agar plate and a tube-plate bacterial count procedure was developed for this group. Procedures for both tests are described and some examples given.

Bacteriological Techniques↗

[Proline arylamidase in human serum].

The catalytic concentrations of proline arylamidase in human sera were determined with L-proline-beta-naphthylamide (endpoint-method) and L-proline-p-nitranilide (continuous reaction). The continuous method was optimized: Tris-HCl, 40 mmol/l, pH 7,2; [S] = 1.53 mmol/l; T = 37 degrees C, t = 5-15 min, no additives. The pH-optimum was found to be 7.20; substrate excess inhibition was not observed. Tris-(hydroxymethyl)-aminomethane und N-morpholino-3-propane sulfonic acid buffers gave similar reaction rates. Reducing substances, SH-reagents, complex-forming or buffer substances, anticoagulants, proteinase inhibitors and the chlorides of Na+, Cu++, Mn++ and Ni++ did not influence the activity of the enzyme. Slight activation by the chlorides of Cd++, Zn++, Hg++, Co++, Mg++ and Ca++ could not be clearly differentiated from the effects of metalloproteinate formation. EDTA and benzethonium chloride inhibited the catalytic activity. In human sera no low molecular weight inhibitors were detectable. Catalytic concentrations were usually in the range below 10 U/l (37 degrees C). The coefficients of variation were found to be 9.1% intraserial and about 14.5% day-to-day. The preliminary upper limit of "normal" range was established as 8.0 U/l (37 degrees C). Comparative simultaneous determinations of the catalytic concentrations, using L-leucine-, L-alanine-, glycine, gamma-L-glutamic- and L-proline-p-nitranilide in the sera of 372 patients, suggest a special diagnostic role for proline arylamidase. The continuous method has been adapted for Vitatron-AKES-Analyser.

Aminopeptidases↗

Measuring urinary protein with the new BioRad reagent kit: evaluation and comparison with five other methods.

Total urinary protein was measured by five methods: BioRad Total Protein Test (TPT), pyrogallol red, benzethonium chloride, sulfosalicylic acid, trichloroacetic acid, and the results compared to those obtained by a method combining preparative ultrafiltration and the biuret reaction. TPT was linear to 1.5 g protein/l, the detection limit 0.0135 g/l, and it was 3-5 times more sensitive than the other methods. Within-day precision (CV) was 4.3%, (0.60 g/l), the day-to-day precision was 4.5%. The protein contents of 35 selected urine samples assigned to one of five groups according to their electrophoretic pattern were assayed by the five methods. No method accurately measured physiological proteinuria, but the values for light chain (Bence Jones), glomerular, tubular and overload proteinurias measured by TPT did not differ significantly from the biuret value. The other methods differed significantly for at least three groups. Alpha 1 acid glycoprotein slightly inhibited TPT, but peptones, amino acids, antibiotics or normal urine constituents had little or no effect. The TPT method has been automated (Kone Progress); normal 24-h urinary protein excretion was 36 mg/day (range 12-114), the protein creatinine ratio was 34 mg/g (12-106 mg/g).

Autoanalysis↗

Wet decontamination-induced stratum corneum hydration--effects on the skin barrier function to diethylmalonate.

Decontamination of chemical agents from the skin uses both dry and wet decontamination processes. Recent studies have shown that wet decontamination frequently results in stratum corneum hydration. To evaluate the hydration effect of wet decontamination on the skin barrier function and hence on the decontamination efficiency, a series of comparative studies were carried out on human skin contaminated with the nerve agent simulant diethylmalonate, using decontamination media having different salinity and surfactants. The results showed that, compared to non-decontaminated skin, remnant diethylmalonate on decontaminated skin penetrated at an accelerated rate in the immediate 2 h following decontamination. This transient enhancement effect, ranging from 20 to 98%, was depended on the nature of the decontamination media used and was more obvious in skin samples that were decontaminated 1 h postexposure. All decontamination media exhibited this effect, with the greatest enhancement observed in the following order: anionic surfactant > cationic surfactant > non-ionic surfactant > deionized water > 0.9% saline > 9% saline.

Aged↗