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At least 19 recordsLinked to original sources
PubMed1997

The effects of hexetidine (Oraldene) on the adherence of Candida albicans to human buccal epithelial cells in vitro and ex vivo and on in vitro morphogenesis.

PURPOSE: This study reports the effects of hexetidine (Oraldene) on two virulence attributes of Candida albicans, namely, in vitro and ex vivo adherence of yeast cells to buccal epithelial cells (BEC) and in vitro morphogenesis. METHODS: The effects of hexetidine treatment of either yeast cells (stationary and exponential phases) or BEC on Candidal adherence, in terms of viable and non-viable adherent yeast cells, were evaluated using an acridine orange stain in conjunction with fluorescence microscopy. Ex vivo anti-adherence effects were determined by rinsing BEC in vivo with hexetidine (0.1%), removal of BEC after defined periods and inclusion in the adherence assay. The effects of hexetidine on morphogenesis were evaluated using light microscopy. Yeast cell viability following exposure to a range of concentration of hexetidine (0.005-0.1% v/v) for defined periods was determined following serial dilution and enumeration on solid media. RESULTS: Treatment of stationary and exponential phase yeast cells or BEC with hexetidine (0.1%) for a range of times (10-300 s) or, alternatively, with a range of concentrations of hexetidine (0.005-0.1%) for a fixed time (30s) significantly decreased the resultant Candidal/ epithelial adhesion. No correlations were observed between reduced adherence and either time of treatment or hexetidine concentration. In vivo treatment of BEC with hexetidine (0.1%) for 30s resulted in prolonged and significant reductions in the ex vivo adherence of both viable and non-viable yeast cells for periods of up to (and including) four hours post-rinsing. Treatment of C. albicans blastospores with hexetidine (0.05, 0.1% v/v) for 10s and 30s totally inhibited Candida morphogenesis, whereas treatment with lower antiseptic concentrations significantly reduced the extent of Candida morphogenesis and the rate of hyphal development. The effects of hexetidine on yeast cell viability were both concentration and time-dependent. CONCLUSIONS: The reduced adherence of C. albicans to BEC and the modification or inhibition of morphogenesis following exposure to hexetidine suggests a clinical role for hexetidine in the prophylaxis of both superficial candidosis and the systemic complications resulting from invasion of sub-epithelial tissue.

Antifungal Agents↗
PubMed2002

Physicochemical characterization of hexetidine-impregnated endotracheal tube poly(vinyl chloride) and resistance to adherence of respiratory bacterial pathogens.

PURPOSE: Ventilator-associated pneumonia is a frequent cause of mortality in intensive care patients. This study describes the physicochemical properties of hexetidine-impregnated poly(vinyl chloride) (PVC) endotracheal tube (ET) biomaterials and their resistance to microbial adherence (Staphylococcus aureus and Pseudomonas aeruginosa). METHODS: PVC emulsion was cured in the presence of hexetidine (0-20% w/w) and was characterized in terms of drug release, surface properties (i.e., microrugosity/contact angle), mechanical (tensile) properties, and resistance to microbial adherence. RESULTS: Under sink conditions, hexetidine release from PVC was diffusion-controlled. Increasing the concentration of hexetidine from 1% to 10% (w/w) (but not from 10% to 20% w/w) increased the subsequent rate of drug release. In general, increasing the concentration of hexetidine decreased both the tensile properties and hydrophobicity, yet increased PVC microrugosity. Following hexetidine release (21 days), the surface properties were similar to those of native PVC. The resistance of hexetidine-containing PVC (1% or 5%) to microbial adherence (following defined periods of drug release) was greater than that of native PVC and was constant over the examined period of hexetidine release. CONCLUSIONS: ET PVC containing 1% (w/w) hexetidine offered an appropriate balance between suitable physicochemical properties and resistance to microbial adherence. This may offer an approach with which to reduce the incidence of ventilator-associated pneumonia.

Analysis of Variance↗
PubMed2000

Determination of the salivary retention of hexetidine in-vivo by high-performance liquid chromatography.

The non-antibiotic antimicrobial agent hexetidine is widely used at a concentration of 0.1% w/v as an oral rinse to reduce the number of viable microorganisms within the oral cavity. However, following use, the available concentration of hexetidine in the oral cavity declines with time, thus compromising the resultant antimicrobial activity. It is, therefore, desirable to determine the persistence of the agent in the oral cavity by quantification of the drug concentration in saliva, thus enabling prediction of its antimicrobial activity in the oral environment. A rapid reverse-phase HPLC method was therefore developed and validated for hexetidine in aqueous solution (Oraldene) and in saliva samples collected from volunteers post-rinsing with 15 mL of hexetidine oral rinse for 30s. The HPLC assay was sufficiently sensitive to accurately detect hexetidine in saliva up to 25 min after in-vivo use of a commercial oral rinse. Furthermore, it was possible to detect hexetidine below the published minimum inhibitory concentrations (MICs) for a selection of microorganisms. From these data a first-order elimination rate constant of hexetidine from the oral cavity was determined post-rinsing in each of six volunteers. The validated HPLC assay method presented is useful for the assay of hexetidine in the oral cavity both at and below MICs. The first-order elimination rate constant shows significant variation between volunteers.

Adult↗
PubMed1997

Protective effect of hexetidine against in vitro bacterial demineralisation of bovine enamel and dentin in the presence of fluoride.

Bovine enamel and dentin specimens were overlaid with acidogenic Streptococcus mutans suspensions in agarose. In this model, the minimal demineralisation-inhibiting concentrations (MDIC) of hexetidine was determined in the presence of fluoride. A commercially available mouthwash containing 0.1% (2.9 mmol/l) hexetidine was diluted serially and added to the bacterial suspensions together with 0, 5.3, or 26.3 mumol/l fluoride (NaF). After 22 h of incubation at 37 degrees C the bacterial suspensions were removed and assessed for calcium and lactate. The results showed significant inhibitory effects of hexetidine on the demineralisation of the enamel specimens with a MDIC between 15 and 31 mumol/l hexetidine. In the presence of fluoride, approximately fourfold higher concentrations of hexetidine were needed for a significant additional protection of the enamel. No synergistic effect between hexetidine and fluoride was observed. For the demineralisation of the dentin specimens, the MDIC of hexetidine had a value between 31 and 61 mumol/l. At both these concentrations the dentin specimens were relatively less protected in the presence than in the absence of fluoride, and some synergistic effect between hexeditine and fluoride was observed.

Animals↗
PubMed1987

The effect of a combination of copper and hexetidine on plaque formation and the amount of copper retained by dental plaque bacteria.

Zn++ in combination with hexetidine exerts a synergistic plaque inhibition. Studies in our laboratory on the mechanism of this effect suggested that Cu++ and hexetidine may have a similar combination effect. This hypothesis was tested in vivo on a human test panel in a double-blind crossover study. The amount of Cu++ retained by plaque bacteria in vitro was also evaluated. Seven volunteers rinsed with the solutions for 1 min twice daily for 5 days. The test solutions were H2O, 1.0 mM CuSO4, 2.0 mM hexetidine, and the last two in combination. During the test period no oral hygiene was allowed, and sucrose-containing chewing gum was used to enhance plaque formation. The plaque index scores after rinsing with the combination were significantly (p less than 0.05) lower than those of the other solutions. The effect of hexetidine on Cu++ retention in plaque bacteria was evaluated in plaque samples (n = 3) grown anaerobically overnight in PPLO medium. The bacteria were washed five times, digested in concentrated HNO3, and Cu++ determined by atomic absorption. The presence of hexetidine resulted in a significantly greater amount of Cu++ retained by bacteria at all CuSO4 concentrations. It is suggested that the nonpolar nature of the hexetidine molecule enables Cu++ bound to hexetidine to pass into the bacterial cell. Within the cell, Cu++ can interfere with bacterial metabolism, giving a reduction in plaque growth.

Adult↗
PubMed1987

Uncoupling of mitochondrial oxidative phosphorylation by hexetidine.

To gain further insight into the biochemical properties of the antibacterial hexetidine, isolated rat liver mitochondria were added with this drug and investigation made of certain features related to mitochondrial bioenergetics. Hexetidine was found to cause oxidation of intramitochondrial pyridine nucleotides and stimulate the rate of oxygen uptake caused by respiratory substrates involving three, two and one site(s) of phosphorylation. Reversal of oxygen uptake inhibition by oligomycin was also determined. By investigating hexetidine effect on oxidative phosphorylation, hexetidine was found both to inhibit the rate of ATP synthesis and to cause ATP hydrolysis. Likewise, hexetidine capability to produce acidification of extramitochondrial medium and to collapse delta psi was also observed. The reported findings show that hexetidine exhibits uncoupling properties.

Adenosine Triphosphate↗
PubMed1991

[The advantage of preventive vaginal antisepsis with hexetidine in obstetrics and gynecology].

In five studies, the advantage of repeated vaginal prophylaxis by a new preparation of hexetidine vaginal suppositories (10 mg) was investigated prospectively, randomised and method-controlled (n = 2 x 50). After a five-day application, the hexetidine group achieved bacterial reductions of five log CFU/ml in the vagina and nearly three log CFU/ml in the cervix uteri, whilst no reduction was found in the controls at any time (p less than 0.01). The reduction of individual bacterial species was investigated in 224 pregnant and also gynaecological patients. In cases of impending preterm childbirth, a five-day application of 20 mg hexetidine/day could reduce all bacteria sufficiently with the exception of lactobacilli; especially beta Streptococci were reduced. The same was achieved by a three-day application of 10 mg hexetidine/day pre-operatively. A long-term study in 11,724 deliveries showed, that neonatal infectious mortality and morbidity after 36 gestational weeks could be reduced significantly by hexetidine. The new hexetidine preparation appeared to be efficient in vaginal antisepsis, especially in pregnancy. A favourable lactobacilli-selective effect was demonstrated. Since the importance of lactobacilli in vaginal ecology is known, hexetidine prophylaxis must be considered as advantageous in Obstetrics and Gynecology. From a practical and economic point of view, the application of hexetidine as vaginal suppositories appears favourable compared to antiseptic solutions.

Adult↗
PubMed2003

Antiplaque and antigingivitis effectiveness of a hexetidine mouthwash.

OBJECTIVE: To assess the antiplaque/antigingivitis efficacy of a hexetidine-containing mouthwash. METHODS: This examiner-blind, parallel group, controlled clinical study examined the effectiveness of a hexetidine (0.1%) mouthwash both in inhibiting the development of supragingival plaque and in reducing gingivitis. One hundred and thirty-four adult subjects completed the 2-week experimental gingivitis model study. Following baseline examinations, which included plaque index, modified gingival index and gingival bleeding index, subjects received a full dental prophylaxis. Subjects were randomly assigned to one of three mouthwashes (hexetidine 0.1%, chlorhexidine 0.12% (positive control) or a 5% hydroalcohol negative control) and commenced three times daily supervised rinsing as their sole method of oral hygiene. All indices were rescored after 2 weeks. RESULTS: Compared to the negative control group, the hexetidine group demonstrated a statistically significant inhibition and reduction of supragingival plaque and gingival inflammation with reductions of 6.3%, 33.5% and 56% for gingivitis, plaque and gingival bleeding, respectively. The results of the chlorhexidine group were used to validate the study. CONCLUSION: The study confirms the efficacy of a hexetidine rinse in reducing supragingival plaque and gingival inflammation.

Adolescent↗
PubMed1981

Comparison of the in vivo and in vitro antibacterial properties of antiseptic mouthrinses containing chlorhexidine, alexidine, cetyl pyridinium chloride and hexetidine. Relevance to mode of action.

A study was carried out to compare the antibacterial properties of four cationic antiseptics, three of which are available as commercial mouthrinse preparations. Minimum inhibitory concentrations for alexidine, cetyl pyridinium chloride, chlorhexidine gluconate and hexetidine against a range of standard test organisms, were determined by tube dilution. Similar values for Oxford staphylococcus were then obtained in Dubos medium to which protein as yeast, or food extract, or serum was added in doubling dilutions to 16%. Salivary bacterial counts after a single rinse with the antiseptics or water throughout the day were measured in 10 subjects together with the duration of any residual antiseptic activity in the saliva. All antiseptics were effective at low concentrations against the organisms tested but the minimum inhibitory concentration values for hexetidine were the highest. Food extract and serum markedly increased the minimum inhibitory concentration values of all antiseptics, although alexidine and hexetidine were the least affected in percentage terms. The activity of a 1% povidone iodine preparation, used for comparison, was almost completely vitiated. An immediate significant fall in salivary bacterial counts was produced by the cationic antiseptics. Return to pre-rinse levels was seen for hexetidine after 90 min, cetyl pyridinium chloride after 3 hours, alexidine after 5 hours and chlorhexidine gluconate after 7 hours. Residual salivary antibacterial activity remained to 90 min for cetyl pyridinium chloride, to 3 hours for hexetidine and alexidine and to 5 hours for chlorhexidine gluconate. The antibacterial properties measured, in particular the duration of effect in vivo, may be relevant to the anti-plaque activity of cationic antiseptics.

Bacteria↗
PubMedDate not supplied

The nitrosation of hexetidine and hexedine: characterization of the major nitrosamine from common antimicrobial agents.

The acidic nitrosation of hexetidine and hexedine, common antimicrobial agents and drug constituents, leads to a mixture of nitrosamines. The major nitrosamine product, "HEXNO", forms rapidly in yields as high as 60% over the pH range 1-4.8 at incubation times of 1 h at 37 degrees C with 40 mM NO2- and 10 mM hexetidine. On the basis of extensive spectroscopic characterization and independent synthesis HEXNO has been assigned the structure of 1-(2-ethylhexyl)-3-nitroso-4-methyl-4-[[N-(2-ethylhexyl)-N- nitrosoamino]methyl]imidazolidine (7). The synthesis of HEXNO involves the novel interception by potassium nitrite in ether/18-crown-6 of an imminium ion produced from the reaction of hexedine with benzyl chloroformate. Collapse of the alpha-amino nitrous ester produced by this reaction yields the nitrosamine containing carbamate 8, which yields HEXNO after removal of the carbamate with trimethylsilyl iodide and subsequent nitrosation. The rapid formation of HEXNO from hexetidine and hexedine supports the hypothesis that tertiary geminal diamines will produce nitrosamines rapidly by a mechanism which involves the cleavage of a nitrosammonium ion with the assistance of the neighboring nitrogen atom. This process is deemed to be of possible importance in the endogenous production of potentially carcinogenic nitrosamines because of its low nitrite requirement and high nitrosation rate. The available data suggest the probable formation of HEXNO and other nitrosamines from hexetidine under conditions of its use.

Chromatography, High Pressure Liquid↗
PubMed1987

Plaque inhibition by hexetidine and zinc.

Rinsing experiments with mouthwashes containing zinc ions, hexetidine and a combination of hexetidine and zinc ions were performed with a group of 10 volunteers. The amount of plaque was assessed after rinsing with the test solutions for 4 days during which mechanical toothcleaning was discontinued. Significantly improved inhibition was observed by the combination of hexetidine and zinc ions compared with the two agents used separately. In vitro bacteriological tests showed that hexetidine and zinc ions had a synergistic inhibitory effect on the growth of Streptococcus mutans.

Dental Plaque↗
PubMed1988

Effects of proprietary oral rinses containing chlorhexidine, hexetidine and benzydamine on the proliferation of human buccal epithelial cells in culture.

Cell cultures were established from small samples of buccal tissue, using a 3T3 fibroblast feeder-layer technique. After exposure to increasing dilutions of three proprietary oral rinses for 22 h or 2 h, the effects upon cell proliferation were studied by measurement of [3H]-thymidine incorporation into cellular DNA. Cell membrane damage was assessed by measurement of lactate dehydrogenase content. Cultures exposed to hexetidine-containing or chlorhexidine-containing rinses for 22 h at dilutions of 250-fold or lower showed almost complete inhibition of [3H]-thymidine incorporation. Cultures treated with benzydamine-containing rinse at the same dilutions showed no significant inhibition of incorporation. Exposure to the same dilutions of hexetidine- and chlorhexidine-containing rinses for 2 h resulted in 65% and 20% inhibition of incorporation, respectively. Lactate dehydrogenase content decreased to negligible levels after exposure to the rinse containing hexetidine at a 250-fold dilution, but was unaffected by the other two rinses. Thus dividing buccal epithelial cells in vitro may be adversely affected by exposure to certain commercial oral rinses.

Benzydamine↗
PubMedDate not supplied

Hexetidine mouthrinse in the management of minor aphthous ulceration and as an adjunct to oral hygiene.

A number of compounds have been used in the management of recurrent oral ulceration, including antimicrobials. This was a double-blind placebo-controlled cross-over study to assess the value of a 0.1% hexetidine mouthwash in the management of minor aphthous ulceration and as an adjunct to oral hygiene. Forty patients with a catalogued history of ulceration took part. Patients were randomly allocated to active/placebo or vice versa order of mouthwashes, which were used as 15 ml volumes three times a day. Treatment periods were 6 weeks with a 3 week washout. During each period patients kept daily records of the number, site, and duration of ulcers, together with pain scores. Plaque and gingivitis were scored at baseline and end of treatment periods. Thirty-eight patients completed the study, with no significant treatment differences between active and placebo rinses on any ulcer parameter. Additionally, the hexetidine rinse provided no significant benefit to oral hygiene or gingival health. However, there was a significant period effect, with considerable ulcer improvements during the second period, irrespective of treatment. In conclusion, the hexetidine rinse appeared to offer no benefits to these patients, but professional supervision of ulcer treatment does appear to result in a worthwhile placebo effect.

Adolescent↗
PubMed1988

Effect of a combination of copper and hexetidine on the acidogenicity and copper accumulation in dental plaque in vivo.

A double-blind crossover study on 4 adult volunteers was performed to evaluate the effect of hexetidine on Cu2+ accumulation in dental plaque as well as a possible enhanced effect of copper on inhibition of acid production in the presence of hexetidine. The experimental period was 5 days. No oral hygiene was allowed, and sucrose-containing chewing gum was used to enhance plaque formation during the test period. In order to evaluate the effect on pH, the test persons rinsed with a 15% glucose (w/v) solution on the 5th experimental day. Plaque pH values recorded before and 5 min after the rinse served as control values. One hour later the test persons rinsed with 10 ml of the test solutions for 1 min. Glucose rinses with pH measurements 5 min after the rinse were carried out 0, 3, and 7 h after the test agents were used. The combination of 1.0 mM copper and 2.0 mM hexetidine gave a significant (p less than 0.05) inhibition of acid production at all times compared both to the controls and to each of the test agents separately. Plaque samples were collected with a toothpick immediately before a 1-min rinse with 10 ml of the test solutions. Subsequent plaque samples were taken 5 min and 3 and 8 h after a rinse from corresponding tooth surfaces. Dry weight was estimated, the plaque bacteria digested by HNO3, and the amount of Cu2+ determined by atomic absorption.(ABSTRACT TRUNCATED AT 250 WORDS)

Acids↗
PubMed1986

Hexetidine ('Oraldene'): a report on its antibacterial and antifungal properties on the oral flora in healthy subjects.

A randomized, double-blind crossover trial, in 10 adult healthy subjects, was carried out to compare the antibacterial and antifungal activity of a 0.1% solution of hexetidine with that of placebo. The pre-dosing oral flora of the subjects was assessed from saliva samples cultured for aerobic and anaerobic bacteria, as well as Candida albicans. Subjects then rinsed their mouths for 1 minute 3-times a day with 15 ml 0.1% hexetidine or placebo, saliva samples being collected at 2 minutes, 30 minutes, 1 hour, 3 hours and 5 hours post-dosing. Dosing was continued for 8 consecutive days on each treatment with an intervening wash-out period of 1 week. Hexetidine reduced aerobic bacterial counts on Day 1 and Day 8 by a maximum of 83% and 86%, respectively, at 2 minutes post-dosing. The reductions were statistically significantly lower than placebo up to 1 hour post-dose on Day 1 and up to 3 hours post-dose on Day 8. Similarly for anaerobic bacterial counts, 92% and 88% maximum reductions were recorded on Day 1 and Day 8, which again were significantly lower than placebo for up to 3 hours post-dose. For Candida albicans, however, the maximum reduction was 91% on the first day and 67% on Day 8, maintained for 30 minutes post-dosing. Although not eradicating completely aerobic and anaerobic bacteria, it is concluded that the substantial reduction in their numbers should prove clinically useful.

Adolescent↗
PubMedDate not supplied

An aziridinium ion intermediate in the nitrosation of a hexetidine model.

The nitrosation chemistry of 1,3,5-trimethyl-5-aminohexahydropyrimidine (2) has been investigated as a model for the behavior of the antimicrobial agent hexetidine (1) under similar conditions. The reaction of 2 with sodium nitrite in glacial acetic acid gives 4-methyl-4-[(methylnitrosamino)methyl]-3-nitroso-1,3-oxazolidine (4) as the major nitrosamine. This compound arises from a molecular rearrangement which proceeds through the diazotization of the primary amino group followed by intramolecular displacement of nitrogen to generate an aziridinium ion. The N-nitrosooxazolidine 4 forms from the nitrosation of an imidazolidine produced from the aziridinium ring hydrolytic opening. The N-nitrosooxazolidine 4, an isomer, 5-methyl-5-[(methylnitrosamino)methyl]-3-nitroso-1,3-oxazolidine (14), which is not formed in the nitrosation of 2, and an analog 4-methyl-4-[[(2-ethylhexyl)nitrosamino]methyl]-3-nitroso-1,3-oxazolidine (22) have been independently synthesized. The N-nitrosooxazolidine 22 which would be formed from hexetidine is not present in its nitrosation mixture, suggesting the absence of reactive aziridinium ions in that case. The dissimilar nitrosation chemistry of 2 and 1 are discussed.

Aziridines↗
PubMed1978

Influence of hexetidine upon plaque and gingivitis in the beagle dog.

Two studies were performed in beagle dogs to determine the effect of 0.2% hexetidine upon plaque and gingivitis. In both instances, hexetidine exerted no significant effect while 0.2% chlorhexidine resulted in reductions in both plaque and gingivitis of about 45 and 50%, respectively.

Animals↗
PubMed1988

Synergistic antibacterial effects of copper and hexetidine against Streptococcus sobrinus and Streptococcus sanguis.

The aim of this study was to determine whether a combination of copper and hexetidine had a synergistic antibacterial effect against Streptococcus sobrinus OMZ 176 and S. sanguis 10556. Concentration ranges of the test agents alone and in combination were prepared by serial dilutions in microtiter trays with brain-heart infusion (BHI) broth as the bacterial growth medium. After incubation at 37 degrees C for 24 h, the minimum inhibitory concentration (MIC), corresponding to the lowest concentration showing no visible growth, was determined. Evaluated by the fractional inhibitory concentration index, a strong synergistic effect ranging from 0.39 to 0.40 was observed. A similar effect was also demonstrated by growth curves, which were constructed on the basis of growth in BHI broth with addition of MIC/4 of each agent alone or MIC/8 of each agent in combination. A probable explanation for these findings is that the surface-active hexetidine molecule alters the bacterial cell surfaces and thereby enables an increased amount of copper to be transported into the cell.

Copper↗