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PubMed1996

The relationship between megacolon and carcinoma of the colon: an experimental approach.

'Carcinoma of the colon does not occur in cases of megacolon' is an axiom held by Brazilian physicians working in endemic areas for Chagas' disease. The objective of the present study was to test this axiom experimentally by submitting rats with experimental megacolon to a carcinogen which causes carcinoma of the colon. Eighty young male Wistar rats received serosal application of either saline (0.9% NaCl) or 2 mM benzalkonium chloride (BAC) to the distal colon. Ten months later randomly chosen saline and BAC rats were injected weekly with dimethylhydrazine (DMH) for 20 weeks. Non-DMH-treated rats from both original groups were maintained, for a total of four experimental groups. Three months after the injections all surviving rats were killed. At autopsy the presence of absence of carcinomas along the colon was recorded. The induction of megacolon was evaluated by morphometry of the wall from the distal colon and myenteric denervation was assessed by neuron counts. An increase of at least 2-fold in distal colon wall thickness confirmed the induction of megacolon in BAC-treated rats. Neuronal counts from BAC and control rats not treated with DMH showed an average denervation of 63%. The number of distal colon carcinomas in BAC+DMH-treated rats was significantly lower than that in DMH-treated rats. These findings appear to contradict the traditional concept of carcinogenesis of the colon. The clinical axiom was reproduced experimentally.

1,2-Dimethylhydrazine↗
PubMed1995

Reducing the risk of Chlamydia trachomatis genital tract infection by evaluating the prophylactic potential of vaginally applied chemicals.

The need to provide women with a partner-independent method of prophylaxis against sexually transmitted disease (STD) against, including Chlamydia trachomatis, has led to a direct effort to develop a vaginally applied, broad-spectrum antimicrobial preparation that is both safe and effective. Using a murine model of C. trachomatis lower genital tract infection, we tested the ability of various vaginally applied chemicals to alter the course of infection in female mice challenged with infectious doses ranging from 10(3) to 10(6) inclusion forming units of an oculogenital serovar of C. trachomatis. When administered in a methylcellulose/propylene glycol-base gel 15 minutes prior to challenge, four widely used topical antimicrobials (benzalkonium chloride, chlorhexidine, nonoxynol-9, and polymyxin B) were shown to protect against infection. These results support the possibility that this type of interventional method may be a clinically relevant means of prophylaxis against sexually transmitted infection with C. trachomatis, the most common bacterial STD agent.

Administration, Intravaginal↗
PubMed1993

Surface antimicrobial activity of heparin-bonded and antiseptic-impregnated vascular catheters.

Most Swan-Ganz pulmonary artery catheters have heparin bonded to the surface with benzalkonium chloride, a cationic surfactant, to reduce thrombosis. Since benzalkonium is bactericidal, the antimicrobial activity of heparin-bonded pulmonary artery catheters was investigated in an in vitro assay. Each catheter exhibited activity against a wide variety of potential microbial pathogens, including Candida albicans. The magnitude of activity against individual organisms correlated strongly with their in vitro susceptibility to benzalkonium chloride (r = .94, P < .002). A chlorhexidine-silver sulfadiazine-impregnated catheter exhibited even greater activity than the heparin-bonded catheters (P = .01). When exposed to serum for 24 h, heparin-bonded catheters lost > or = 50% of their antimicrobial activity, whereas the activity of the chlorhexidine-silver sulfadiazine-impregnated catheter was minimally affected. The fortuitous surface antimicrobial activity of heparin-bonded catheters may account for the low incidence of catheter-related bacteremia (mean, 1.0%) compared with Swan-Ganz catheters of the same materials but not coated with benzalkonium-heparin (mean, 2.8%).

Benzalkonium Compounds↗
PubMed1985

Antiseptic-induced changes in the cell surface of a chlorhexidine-sensitive and a chlorhexidine-resistant strain of Providencia stuartii.

The effects of chlorhexidine diacetate and benzalkonium chloride on the cell surface of a chlorhexidine-sensitive (Pv 2) and a chlorhexidine-resistant (Pv 67) strain of Providencia stuartii are described. Low concentrations of chlorhexidine diacetate (10 mg/l and upwards) increased the hydrophobicity of Pv 2, whilst having little effect on Pv 67. Both strains were resistant to benzalkonium chloride but a concentration as low as 2 mg/l induced a significant increase in hydrophobicity in Pv 2, with 25-50 mg/l needed to induce a similar type of increase in Pv 67. The possible nature of the resistance is discussed.

Anti-Infective Agents, Local↗
PubMed1993

A novel antimicrobial central venous catheter impregnated with benzalkonium chloride.

Catheter-related sepsis is a common complication associated with the use of central venous catheters (CVC). In an attempt to overcome this problem benzalkonium chloride was incorporated into a CVC polymer. The effect of the presence of benzalkonium chloride on microbial colonization of the CVC was then assessed in vitro. MICs and MBCs of benzalkonium chloride for a range of organisms were performed and good activity against Gram-positive organisms was confirmed. In order to assess the antimicrobial activity of the benzalkonium-chloride-impregnated catheter, 2 cm lengths were placed on to nutrient agar plates inoculated with various micro-organisms. Zones of inhibition against five strains of Staphylococcus epidermidis and two strains of Staphylococcus aureus were demonstrated. Smaller zones of inhibition was also produced with Gram-negative species and Candida albicans. The zone sizes correlated with the MICs. Bacterial adherence to the benzalkonium-chloride-impregnated catheters was determined in both static and dynamic models and was significantly reduced compared with control catheters, containing no antimicrobial agent (P < 0.01). Inhibition of microbial adherence to benzalkonium-chloride-impregnated catheters placed in 25% human blood in phosphate-buffered saline (PBS), for up to seven days or PBS alone for 14 days was detected. The findings indicate that benzalkonium-chloride-impregnated catheters exhibit reduced microbial colonization by a range of organisms in vitro. The incorporation of benzalkonium chloride into a CVC may thus offer an effective method for the prevention of catheter related sepsis.

Bacteria↗
PubMed1993

The inhibitory effect of spermicidal agents on replication of HSV-2 and HIV-1 in-vitro.

Five spermicides including nonoxynol-9 were assessed under in-vitro conditions, for their inhibitory activity against two viruses capable of spread by sexual intercourse, herpes simplex virus type-2 (HSV-2) and the human immunodeficiency virus type-1. A further eight commercially-available spermicidal preparations containing varying concentrations of either nonoxynol-9 or nonoxynol-11 were also assessed for activity against HSV-2. All spermicides and spermicidal preparations tested showed inhibitory activity against both viruses over periods of time ranging from 30 sec to 5 min. This activity was dependent on the concentration of spermicide to which the viruses were exposed.

Antiviral Agents↗
PubMed2000

Emergence of resistance to biocides during differentiation of Acanthamoeba castellanii.

A synchronous encystment method was used to study the order of development of resistance of Acanthamoeba castellanii to a range of biocides. The emerging resistance during encystation to short-term exposure to the minimum amoebicidal concentrations of each biocide tested was recorded during the first 36 h of the differentiation process. Hydrochloric acid and moist heat were tested as possible resistance markers. Development of the acid-insoluble, proteincontaining, ectocyst wall and the cellulose endocyst wall was followed by quantification of the acid- and alkali-insoluble residues of cell samples removed from synchronous encystment cultures up to 36 h. Resistance to chemical agents (polyhexamethylene biguanide, benzalkonium chloride, propamidine isethionate, pentamidine isethionate, dibromopropamidine isethionate, hydrogen peroxide) and to moist heat was seen to develop between 14 and 24 h after trophozoites were inoculated into the encystment media. Resistance to hydrochloric acid developed between 0 and 2 h and to chlorhexidine diacetate between 24 and 36 h. Levels of acid-insoluble residues began to increase after 8 h and alkali-insoluble residues (cellulose) were detected after 16 h and coincided with the emergence of resistance to all the agents tested except hydrochloric acid. The results suggest that resistance to the biocides tested probably results largely from the physical barrier of the cyst walls rather than as a consequence of a metabolically dormant cyst.

Acanthamoeba↗
PubMed2000

In vitro inactivation of Chlamydia trachomatis and of a panel of DNA (HSV-2, CMV, adenovirus, BK virus) and RNA (RSV, enterovirus) viruses by the spermicide benzalkonium chloride.

Kinetics of inactivation by the detergent spermicide benzalkonium chloride (BZK) of Chlamydia trachomatis and of a panel of DNA viruses [herpes simplex virus hominis type 2 (HSV-2), cytomegalovirus (CMV), adenovirus (ADV) and BK virus (BKV)] and RNA [respiratory syncytial virus (RSV) and enterovirus (ENV)] were established in accordance with a standardized in vitro protocol. After a 5 min incubation, inactivation of >95% of HSV-2 and CMV was obtained at a concentration of 0.0025% (w/v) (25 Ig/L); concentrations as low as 0.0005%, 0.0050% and 0.0125%, induced a 3.0 log10 reduction in infectivity of HSV-2 and CMV, RSV and ADV, respectively. After a 60 min incubation, concentrations of 0.0125% and 0.050% provided a 3.0 log10 reduction in infectivity of ENV and BKV, respectively. These features indicate that sensitivity to BZK was very high (HSV-2 and CMV) or high (RSV) for enveloped viruses, intermediate (ADV) or low (ENV and BKV) for non-enveloped viruses. Furthermore, BZK had marked antichlamydial activity, showing >99% killing after only a 1 min incubation at a concentration of 0.00125%. BZK demonstrates potent in vitro activity against the majority of microorganisms causing sexually transmitted infectious diseases, including those acting as major genital cofactors of human immunodeficiency virus transmission. These attributes qualify BZK as a particularly attractive candidate for microbicide development.

Adenoviridae↗
PubMed2003

Treatment of plastic and extracellular matrix components with chlorhexidine or benzalkonium chloride: effect on Candida albicans adherence capacity in vitro.

This study investigates the influence of treatment of plastic and extracellular matrix (ECM) proteins with chlorhexidine or benzalkonium chloride on subsequent adherence of Candida albicans. Three concentrations were tested for each antiseptic: (i) chlorhexidine, MIC (6.25-12.5 mg/L), 80 x MIC and 800 x MIC; and (ii) benzalkonium chloride, MIC (3.12 mg/L), 40 x MIC and 1600 x MIC. Chlorhexidine and benzalkonium chloride activities were correlated with the tested concentrations. Antiseptics used at MIC were unable to modify the adherence to plastic or ECM proteins. Chlorhexidine (80 x MIC) induced a decrease in plastic adherence of 31% of the 15 strains used and an increase in ECM protein adherence of 13% of strains. Benzalkonium chloride (40 x MIC) induced a decrease in adherence to ECM proteins or plastic of 13-27% of strains. Our results indicated that the treatment with 1600 x MIC benzalkonium chloride could induce the opposite effect on adherence, depending on the surface: 60% of the strains showed an increase in their adherence to ECM proteins, whereas 93% of the strains showed a decrease in their adherence to plastic. A similar phenomenon was observed after treatment with 800 x MIC chlorhexidine: 60% of the strains showed an increase in their adherence to ECM proteins, whereas 67% showed a decrease in adherence to plastic. Treatment of medical devices with at least 5000 mg/L of chlorhexidine or benzalkonium chloride could therefore reduce C. albicans adherence to plastic surfaces, but would be unable to prevent fungal adherence to ECM proteins.

Anti-Infective Agents, Local↗
PubMed2006

In vitro antimicrobial activity of benzalkonium chloride against clinical isolates of Streptococcus agalactiae.

OBJECTIVES: Despite antibiotic prophylaxis for at-risk mothers during labour and delivery, Streptococcus agalactiae (group B Streptococcus; GBS) still causes substantial morbidity and mortality among newborns. In addition to the well-known side effects of the administration of antibiotics, resistance to drugs recommended for penicillin-allergic pregnant women, such as erythromycin and clindamycin, has increased, thus raising concern about the possibility of inadequate prophylaxis. On this basis we evaluated the antimicrobial activity of benzalkonium chloride against GBS, which has been described as an antimicrobial agent for the topical treatment of vaginal infections. METHODS: A total of 52 GBS from pregnant women have been studied. The capacity of benzalkonium chloride as well as of penicillin, erythromycin, clindamycin, vancomycin, chloramphenicol and tetracycline to inhibit GBS was evaluated using broth macrodilution and microdilution methods, respectively. RESULTS: While all the strains were penicillin- and vancomycin-susceptible, 19.2% were resistant to both erythromycin and clindamycin. In contrast, all GBS isolates were either inhibited or killed by benzalkonium chloride at not only low but also very similar concentrations (MIC90 = 3.12 mg/L). CONCLUSIONS: Benzalkonium chloride might represent an alternative strategy that is useful in reducing vaginal GBS colonization in pregnant women before delivery by topical treatment.

Anti-Infective Agents, Local↗
PubMed1994

Effects of cholic acid and 'Protectaid' formulations on human sperm motility and ultrastructure.

Cholic acid (sodium cholate) and the other active ingredients of F-5 gel preparations in use for the impregnation of a new vaginal sponge (Protectaid) with contraceptive and anti-sexually transmitted disease properties, were assessed for their effects on human sperm motility and ultrastructure. Cholic acid (CA) produced an inhibition of motility which was both dose- and time-dependent. A complete suppression of motility was obtained at 30 s by a CA concentration of 1.25%. Nonoxynol-9 (NX9) compared with benzalkonium chloride (BZC) showed no significant difference at the concentration required (0.025%) to give a total inhibition of sperm motility after exposure for 30 s. The addition of F-5A gel containing 0.5% of each one of the spermicide ingredients (CA, NX9 and BZC) produced the total suppression of sperm motility within 30 s at a dilution of 1/50. Another preparation, F-5B gel, containing the spermicide ingredients at different concentrations (1.25% CA, 0.125% NX9 and 0.05% BZC) produced this same effect with a 1/10 dilution. Exposure of semen to a CA concentration of 1.25% or to 1/10 dilutions of F-5A gel for 30 s led to profound changes of sperm ultrastructure studied by scanning (SEM) and transmission (TEM) electron microscopy. SEM and TEM findings indicate that CA acts as a spermicide through its 'natural detergent' properties, damaging the outer plasma membrane of sperm cells. Protectaid formulations affect sperm motility and viability in a similar way.

Acrosome↗
PubMed1999

Methemoglobinemia induced by topical anesthesia: a case report and review.

Topical anesthetic drugs are widely used by clinicians during hospital and outpatient procedures and are also available to the public in a variety of over-the-counter preparations. Although generally safe, they may cause potentially life-threatening methemoglobinemia. We describe a patient who developed repeated episodes of severe methemoglobinemia after administration of topical Cetacaine spray (a proprietary mixture of benzocaine, tetracaine, and butamben) employed for pharyngeal anesthesia before endotracheal intubation, and briefly review the etiology and pathophysiology of this disorder. Cautious interpretation of oxyhemoglobin saturation values obtained by pulse oximetry or estimated from arterial blood gas analysis is crucial lest the diagnosis of severe methemoglobinemia and the resulting hypoxemia are overlooked. If necessary, the condition is usually readily corrected by intravenous administration of methylene blue.

4-Aminobenzoic Acid↗