Benzalkonium Chloride Solution Research Articles

Enteric Neuronal Ablation: Structure–Activity Relationship in a Series of Alkyldimethylbenzylammonium Chlorides

Serosal application of a commercial solution of benzalkonium chloride (BAC) has been shown to selectively ablate myenteric neurons in the rat jejunum. This experimental model has proven useful in the study of the role of the myenteric plexus in intestinal function. The commercial BAC is a mixture of at least three homologous N-alkyldimethylbenzylammonium chlorides (ADBAC). The purpose of this study was to determine neuronal ablative activity in a series ofADBAC homologs when applied on the serosa of rat jejunum. Homologs not commercially available were synthesized and purified. Seven ADBAC homologs with alkyl chain lengths ranging from C6 to C18 were tested. A solution of each homolog (2 mM in saline) was applied directly on the serosa of an exteriorized portion of jejunum from anesthetized rats. Fifteen days after treatment, animals were sacrificed and treated tissues were processed for neuronal cell counts and muscle thickness determinations. All ADBAC homologs, except C18, ablated neurons of the myenteric plexus and produced thickening of intestinal smooth muscle. The number of submucosal neurons was not affected by any of the homologs. The structure-activity relationship observed in this study paralleled that of the reported antimicrobial activity of the ADBAC homologs, and is related to the aqueous solubility and relative surface activities of the homologs. The C14 homolog was found to be the most effective ablative agent, and reduced the number of myenteric neurons in a concentration-dependent manner. Thus, the C14 homolog can be used to produce a selectively denervated jejunal model for use in acute or chronic in vitro or in vivo studies of intestinal function.

Effect of chemical ablation of myenteric neurones on intestinal cell proliferation.

The duodenum or descending colon of male Wistar rats (average weight 60 g) was treated by a serosal application of a 0.2% solution of benzalkonium chloride (BAC) for 30 min. Control animals were treated with 0.9% (physiological) saline. The rats were allocated to four groups: Group DC (N = 8) in which the duodenum was treated with physiological saline; Group DB (N = 8) in which the duodenum was treated with BAC; Group CC (N = 7) in which the descending colon was treated with physiological saline and Group CB (N = 7) in which the descending colon was treated with BAC. After treatment, the animals were followed up for 5 months. At the end of the experiment, the animals were injected intraperitoneally with vincristine sulphate before sacrifice. Three segments were removed from the duodenum and descending colon for neuronal counting, catecholamine and serotonin measurements and morphokinetic studies of the epithelium. The following results were obtained: (1) there was a significant reduction in neurone number in the myenteric plexus of segments treated with BAC; (2) in the denervated intestinal segments, catecholamine levels were unchanged whereas serotonin levels were increased; (3) epithelial hyperplasia was observed in the denervated duodenum and descending colon; and (4) crypt cell production rate in the duodenum was similar in groups DC and DB but was significantly increased in the descending colon in group CB as compared with controls (CC). The present findings indicate that selective myenteric neuronal denervation caused by benzalkonium chloride plays a causative role in the hyperplasia and crypt cell production rate of the intestinal epithelium (duodenum and descending colon). These changes are probably induced by functional imbalance by the surviving neuronal elements in the gut, implicating neurotransmitters such as acetylcholine, noradrenaline, serotonin, somatostatin and vasoactive intestinal peptide.

Evaluation of rapid drying hand disinfectant preparations in the intensive care unit.

MK412A (0.2% chlorhexidine in 70% ethanol) and MK412B (0.2% benzalkonium chloride in 70% ethanol), which are rapid drying and rubbing antiseptic preparations, have been evaluated for hand sterilization over a month by ICU nurses. They have been shown to have effective skin decontaminant efficacy under practical conditions in a busy ICU. There were no adverse reactions except for two cases of mild erythema in the MK412A treatment group. In a comparative in vitro study with Pseudomonas cepacia, 0.2% chlorhexidine solution alone and 0.2% benzalkonium chloride solution alone were less bactericidal than MK412A and MK412B.

Embryotoxicity of benzalkonium chloride in vaginally treated rats.

The effects of the spermicide benzalkonium chloride (BKC) were studied on the conceptus of rat. Single doses (0, 25, 50, 100 or 200 mg kg-1) of aqueous solutions of BKC were administered intravaginally (1 ml kg-1) on gestational day 1. The vulval metallic clips, used to prevent leakage of the solution, were removed 24 h post-treatment. Fetuses were obtained and examined for malformations on day 21 of gestation. slight to copious amounts of vaginal discharge and vaginitis were noticed in rats treated with the two largest doses of BKC. A dose-related increase in resorptions and fetal death, reduction in litter size and weight were observed in BKC-treated dams. The conceptus loss seemed to occur both before and after implantation. BKC did not cause any discernible visceral malformations, although minor sternal defects occurred in fetuses exposed to 100 and 200 mg kg-1 of the spermicide. These results suggest that single vaginal application of BKC is embryo- and fetocidal in the rat at a dose about 143 times higher than that recommended for controlling conception in women.

Experimental studies on intestinal absorption following Martin's operation.

Experimental studies were done on rats on compensatory absorptive capacity following Martin's operation for extensive aganglionosis. Experimental aganglionosis was produced in the descending colon of rats by serosal application of 0.1% benzalkonium chloride solution. Wide side-to-side anastomosis was performed between the aganglionic colon and the distal ileum, removing the remaining colon. As to absorptive capacity of water and electrolytes, this experimental intestine was compared, with other intestines, especially control intestine, in which similar side-to-side anastomosis was done between the normal colon and the normal ileum. "Experimental" as well as control intestine showed higher absorptive capacities of water, Na and Cl per unit length than did summed up values of the ileum and the colon per unit length. Postoperative body weight curves showed fairly good increases and appearance of feces showed a fair improvement in the experimental group. Autopsy of experimental intestine revealed marked dilatation of the anastomosed ileum and mucosal hypertrophy of the anastomosed colon. These results suggested a favorable compensatory absorptive capacity following Martin's operation.

Forensic Chemical Studies on Drugs. V. Gas Chromatographic Analysis of Benzalkonium Chloride

Benzalkonium chloride used as detergents and disinfectants was readily analyzed by gas chromatography (GC) of their reduction products obtained by their treatment with NaBH4 and NiCl2. The reduction products of benzalkonium chloride (alkyldimethylbenzylammonium chloride) were identified as alkyldimethylamines (I-VI) by GC-mass spectrometry. In the reduction, the benzyl groups of alkyldimethylbenzylammonium chloride was eliminated as toluene. The procedure is applicable for characterizing the distribution of long chain alkyl groups in benzalkonium chloride, and suited for the assay of 10-100 μg/ml aqueous solution of benzalkonium chloride (mainly consisting of the n-C12H25, n-C14H29 and n-C16H33 homolog components : Zephiran). Furthermore, the procedure is very useful for routine analysis of benzalkonium chloride since the reduction takes place smoothly by the use of NaBH4 and NiCl2 which are relatively safe to handle and inexpensive, instead of a complicated apparatus and expensive catalyst in catalytic hydrogenation.

On the pathogenesis of intestinal aganglionosis. A consideration based on electron microscopic observations of experimental and clinical aganglionoses.

A close resemblance in fine structure was observed between the aganglionic colon, produced in rats by serosal application of 0.1% benzalkonium chloride solution, and the aganglionic descending colon, or more proximal segments, of Hirschsprung's disease. The pathogenesis of the disease is discussed.

Increased corneal permeability induced by the dual effects of transient tear film acidification and exposure to benzalkonium chloride

A number of common eyedrop solutions were found to be at acid pH and to have considerable acidic buffering capacity. Rabbit tears were shown to have weak buffering capacity at physiologic pH; a single drop of acidic ophthalmic preparation markedly reduced tear film pH for 10 to 15 min. One drop of pH 4 buffer eyedrop without other components reduced rabbit tear film pH in vivo by the same magnitude as the ophthalmic formulations; depressed pH persisted for at least 5 min. To assess the integrity of the corneal epithelial barrier after exposure to transiently acidified tear film, trace amounts of [ 14C]inulin were added to buffer solutions and the inulin concentrations in cornea and aqueous humor determined as 14C (d/min)/mg. Even 15 min after a pH 4 buffer eyedrop, mean corneal inulin concentration was three times that in pH 7 buffer-treated eyes. A concomitant increase in aqueous humor inulin concentration was observed. Corneal permeability was also assayed with the [ 14C]inulin instilled 15 min after application of a buffered eyedrop containing either 0·01 or 0·02% benzalkonium chloride, a common eyedrop preservative. In neutral pH solution, 0·01% benzalkonium chloride did not alter corneal permeability significantly, but the 0·02% solution increased corneal inulin concentration by a factor of seven compared to controls. In pH 4 buffer, however, both the 0·01% and 0·02% benzalkonium chloride solutions increased corneal inulin penetration—by tenfold and eighteenfold, respectively. Thus, the combined effects of acid buffering and benzalkonium chloride on corneal permeability were more than double the effects of either one alone.

THE PREPARATION OF A STABLE FORMULATION FOR TRIFLUOROTHYMIDINE EYE-DROPS

Summary Dry and moist heat are shown to be unsuitable for the sterilization of trifluorothymidine eye-drops and such preparations must be sterilized by aseptic filtration. The solution is freeze-dried following filtration and the eye-drops reconstituted by the addition of 0.1% w/v benzalkonium chloride solution. The freeze-dried preparation is given a 2 vear shelf life.

Control of Cross-Contamination

High-speed, air-driven handpieces and dental burs are contaminated after use and thus they can be a source of cross-contamination of patients. The effectiveness of the disinfectant solutions of benzalkonium chloride and aqueous activated 2% glutaraldehyde was compared in tests involving suspensions of two microorganisms. The glutaraldehyde solution was bacteriocidal within five minutes in tests involving Streptococcus pyogenes, and within three hours in tests with Bacillus stearothermophilus. Benzalkonium chloride appeared to be less effective.

Disinfection of the skin: an assessment of some new preparations.

Repeated hand washing with a detergent solution containing 0.75% chlorhexidine digluconate was found to cause a large reduction in the resident skin flora which was slightly though significantly smaller than that caused by the use of 3% hexachlorophane liquid soap containing a phenolic preservative, chlorocresol 0.3%. Both agents caused a greater immediate reduction of bacteria after a single hand washing than the hexachlorophane liquid soap without a phenolic additive had shown in earlier experiments; the soap base containing chlorocresol 0.3% but no hexachlorophane was also found to cause a large reduction in skin flora. The chlorhexidine detergent solution had no residual disinfectant action on the skin after rinsing and drying the hands.Disinfection of an operation site for two minutes with povidone-iodine containing 1% available iodine in 70% ethyl alcohol caused about as great a reduction in resident flora as a similar treatment with alcoholic 0.5% chlorhexidine. Both treatments were more effective than disinfection with aqueous 1% cetrimide or 0.1% benzalkonium chloride solutions.

Resistance of Pseudomonas to quaternary ammonium compounds. I. Growth in benzalkonium chloride solution.

Resistant cells of Pseudomonas aeruginosa and a waterborne Pseudomonas sp. (strain Z-R) were able to multiply in nitrogen-free minimal salts solution containing various concentrations of commercially prepared, ammonium acetate-buffered benzalkonium chloride (CBC), a potent antimicrobial agent. As the CBC concentration increased, growth increased until a point was reached at which the extent of growth leveled off or was completely depressed. Minimal salts solutions of pure benzalkonium chloride (PBC) containing no ammonium acetate did not support bacterial growth. When ammonium acetate was added to PBC solutions in the same concentrations found in CBC solutions, growth patterns developed that were comparable to those found with CBC. Likewise, (NH(4))(2)SO(4) added to PBC solutions supported growth of both organisms. P. aeruginosa was initially resistant to CBC levels of 0.02% and it was adapted to tolerate levels as high as 0.36%. Strain Z-R was naturally resistant to 0.4% CBC. Since ammonium acetate, carried over by the CBC used in drug formulations and disinfectant solutions, has the potential to support the growth of resistant bacteria and thus make possible the risk of serious infection, it is suggested that regulations allowing the presence of ammonium acetate in CBC solution be reconsidered.

Resistance of Pseudomonas to Quaternary Ammonium Compounds. I. Growth in Benzalkonium Chloride Solution

Resistant cells of Pseudomonas aeruginosa and a waterborne Pseudomonas sp. (strain Z-R) were able to multiply in nitrogen-free minimal salts solution containing various concentrations of commercially prepared, ammonium acetate-buffered benzalkonium chloride (CBC), a potent antimicrobial agent. As the CBC concentration increased, growth increased until a point was reached at which the extent of growth leveled off or was completely depressed. Minimal salts solutions of pure benzalkonium chloride (PBC) containing no ammonium acetate did not support bacterial growth. When ammonium acetate was added to PBC solutions in the same concentrations found in CBC solutions, growth patterns developed that were comparable to those found with CBC. Likewise, (NH(4))(2)SO(4) added to PBC solutions supported growth of both organisms. P. aeruginosa was initially resistant to CBC levels of 0.02% and it was adapted to tolerate levels as high as 0.36%. Strain Z-R was naturally resistant to 0.4% CBC. Since ammonium acetate, carried over by the CBC used in drug formulations and disinfectant solutions, has the potential to support the growth of resistant bacteria and thus make possible the risk of serious infection, it is suggested that regulations allowing the presence of ammonium acetate in CBC solution be reconsidered.

Benzalkonium Chloride Solution as a Source of False Proteinuria

A source of false proteinuria was recently discovered when two female children were noted to have heavy "proteinuria" in clean voided urine specimens obtained in the Children's Service Ambulatory Clinic. The girls were admitted to the hospital a few days later. Repeated urine specimens were negative for protein in the hospital. In an effort to explain this discrepancy, 5 drops of 10% sulfosalicylic acid were added to benzalkonium chloride solution which is routinely used to clean the genitalia in the [See Table I in Source Pdf.] Children's Clinic but not used on the wards. The benzalkonium chloride-sulfosalicylic acid mixture gave a 4+ precipitate indistinguishable from the 4+ protein reaction.

Benzalkonium chloride as a source of infection.

BENZALKONIUM chloride is widely used as a germicide in clinical medicine. When used correctly it is an agent of proved effectiveness, but its misuse can result in severe and even fatal infections.1 This study records 2 separate incidents at Walter Reed Army Hospital occurring approximately a year apart in which benzalkonium chloride¶ was incriminated as the source of contamination. In the first incident, 11 patients from the gastrointestinal and hematologic wards apparently acquired infections from solutions of benzalkonium chloride that were used for skin disinfection. The second incident occurred in the delivery room, but no known infections were recorded, mainly . . .

Anesthesia and antisepsis with benzalkonium chloride (zephiran) ice cubes.

Chilling the skin with an ice cube of 1:1000 aqueous benzalkonium chloride (Zephiran) gives quick, painless, superficial anesthesia plus antisepsis. No other steps are necessary prior to minor electro-surgery. Numbing a proposed injection site with an ordinary ice cube is an old pediatric procedure. Prior to electrosurgery, however, an alcohol sponge could not be used to wipe the skin without a flash fire from the spark. Breaking the skin contaminated with unsterile water from an ordinary ice cube might be objectionable. To overcome these objections, I make ice cubes by diluting 4 cc. of stock aqueous 12.8% commercial concentrate of benzalkonium chloride with 500 cc. of water. This makes one tray (14 ice cubes) of 1:1000 benzalkonium chloride solution, * costing 1/5¢ per cube. An added drop or two of any dye (gentian violet, Parker 51 ink, methylene blue, etc.) protects the staff from inadvertently drinking benzalkonium chloride ice cubes

口内接近法による犬及猫に於ける下垂体剔出術

An improved technique for the hypophysectomy in dogs and cats is described. This is a modification of McLean's buccal method in dogs. The operation is performed under the barbiturate anaesthesia in dogs and by the subcutaneous injection of ether in cats. No assistant service is neccessary. The benzalkonium chloride solution is adopted to simplify the sterilization of instruments, gauze, cotton and operative field. Characteristic advantages of this technique are as follows. A clod of clay wrapped in a sterilized vinyl sheet is used conveniently for the head fixation. Three kinds of hooks are used snugly for drawing the tongue, for lateral retraction of the incised edges of the soft palate and of the freed edges of the mucoperiosteum of the sphenoid bone. A clear-cut oval hole is produced in the sphenoid bone by the dental points (No. 9 & 20). Accordingly the gauge and the mallet are -not neccessary throughout the perforation. Moreover the dental points will serve to prevent the bleeding in the diploe. A very small steel plate probe is convenient to separate the pituitary from the attachment to the diaphragma sellae. The stalk section before the suction of pituitary will protect the hypothalamus from injury. After the removal of the pituitary the defect hole is filled with penicillin. The nasopharyngeal mucous membrans is sutured and it is not neccessary to close the periosteum.In cats and puppies the haemorrhage in the diploe is generally rare, so that the operation will be very easy. In some dogs, however, the haemostasis during perforation may prove to be tedious, although it will not make the pituitary extirpation itself impossible. Even if operative procedures through the dura opening extend beyond 1 hour by some accidents, the danger of meningitis would be prevented by the local and systemic administration of penicillin.The average duration of this operation are about 1 hour or less, 1 to 2 hours and 3 hours or more, respectively, in cats, puppies and dogs. In view of the simplicity and the short duration of the operation and additionally rapid recovery, this technique would be most suitable in cats and puppies.